Premise.

In the near future, physicist Dr. Sam Beckett (Bakula) theorized it is possible to time-travel within one's own lifetime, and obtains government support to build his project "Quantum Leap". Some years later, the government threatens to pull funding as no results have been made, and Sam decides to test the project accelerator by himself to save the project before anyone can stop him. He is thrown back in time, and on gaining consciousness, finds that while he physically exists in the past, he appears to everyone else as a person that he had "leapt" into and further has partial amnesia related to his own identity. A hologram of his friend, Admiral Al Calavicci (Stockwell), appears, visible and audible only to Sam, and helps to explain to Sam that he must correct something that went wrong in the past, aided with the resources of the project's supercomputer Ziggy (voiced by Pratt), as once that is corrected, he should be able to leap back to the present. Despite successfully correcting the past, Sam continues to leap randomly to another place and time within the second half of the 20th century, "putting things right that once went wrong and hoping each time that his next leap will be the leap home".

Cast and characters.

In each episode, a different cast of guest characters appears, mostly the ones whom Sam replaces with his leaps. Several other characters are referred to regularly throughout the series, but are mostly unseen.

Production.

Development.

The main premise for "Quantum Leap" was inspired by such movies as "Heaven Can Wait" and "Here Comes Mr. Jordan", as well as the 1960s TV show The Time Tunnel. It also may have evolved out of an unused Battlestar Galactica story that was proposed for the "Galactica 1980" series. Series creator Donald P. Bellisario saw its concept as a way of developing an original anthology series, as anthologies were unpopular with the networks.  The series ran on NBC for five seasons, from March 1989 through May 1993.

Soundtrack.

The theme for the series was written by Mike Post. It was later rearranged for the fifth season, except for the series finale episode, which featured the original theme music. Scores for the episodes were composed by Post and Velton Ray Bunch.  A soundtrack album was first released in 1993, titled "Music from the Television Series 'Quantum Leap' ", dedicated to John Anderson, who played Pat Knight in "The Last Gunfighter". It was released by GNP Crescendo on CD and cassette tape.

Episodes.

Broadcast history.

The "Quantum Leap" series was initially moved from Friday nights to Wednesdays. It was later moved twice away from Wednesdays to Fridays in late 1990, and to Tuesdays in late 1992. The series finale aired in its Wednesday slot in May 1993.  The most frequent time slot for the series is indicated by "italics":  In the United Kingdom, the show began on BBC Two on February 13, 1990, airing Tuesday evenings at 9:00 pm. The final episode was scheduled to be aired on June 14, 1994, but altered schedules after the death of British dramatist Dennis Potter earlier that month delayed the airing until June 21, 1994. Repeat episodes continued on the channel at various times until December 28, 1999.

Home media.

Universal Studios has released the entire, digitally remastered, "Quantum Leap" series on DVD. Some controversy arose when fans discovered that many songs had been replaced from the soundtrack due to music rights issues. For the fifth season, Universal included all of the original music. Music Replacement in Quantum Leap – Quantum Leap Podcast Quantum Leap on DVD: The Missing Music List (Seasons 1-4) - Al's Place Quantum Leap Online Community  On April 13, 2016, Mill Creek Entertainment announced that it had acquired the rights to the series and re-released the first two seasons on DVD on June 7, 2016.  On February 7, 2017, Mill Creek re-released "Quantum Leap - the Complete Series" on DVD and also released the complete series on Blu-ray for the first time. The 18-disc set contains all 97 episodes of the series, as well as most of the original music restored for all seasons.

Final episode.

At the end of season five, Bellisario was told to write an episode that could serve as a season finale or series finale, as whether " Quantum Leap" would be renewed was unclear. The episode contained some answers to long-standing questions about the show, but contained enough ambiguity for a season six. However, when the show was not renewed, two screenshots were tacked on to the end of the last episode; one read that Al’s first wife Beth never remarried, so they were still married in present day and had four daughters. The last screenshot said Sam never returned home. The finale was met by viewers with mixed feelings.  A few years after the airing of the finale, a script for an alternate ending was leaked on the internet. It implied that Al, through encouragement of his wife Beth, would become a leaper to go after Sam and that they would be leaping into the future. Bellissario has said no script exists and that he does not know where this idea came from. However in 2018, fan Allison Pregler purchased screen shots taken from season five that contained some shots of Al and Beth together; this implies that part of the alternate ending was, in fact, shot and gives credibility to the alternate-ending scenario. In May 2019, a video of the lost footage was actually uploaded to Reddit by a contributor with the handle Leaper1953. How this person obtained the footage is not known publicly. Scott Bakula confirmed that several endings were shot and that the footage was authentic.

Reception.

Despite its struggling start with poor broadcast times, the series had gained a large 18–49 demographics of viewers. The finale was viewed by 13 million American households. In 2004 and 2007, "Quantum Leap" was ranked number 15 and 19, respectively, on "TV Guide's ""Top Cult Shows Ever".

Awards.

Along with 43 nominations, "Quantum Leap" received 17 awards (listed below).

Other media.

Comics.

Innovation Publishing produced a series of comic books that ran for 13 issues from September 1991 through August 1993. As with the television series, each issue ended with a teaser preview of the following issue and Sam's exclamation of "Oh, boy." Among the people into whom Sam found himself leaping in this series were:  Few of the comic stories referenced episodes of the television series, with the exception of the ninth issue, "Up Against a Stonewall".

Possible continuation.

Occasional announcements of plans to revisit or restart the series have been made. In July 2002, the Sci-Fi Channel announced its development of a two-hour television film based on "Quantum Leap", which it was airing in reruns at the time, that would have served as a backdoor pilot for a possible new series, with Bellisario as executive producer. During the "TV Guide" panel at the 2010 San Diego Comic-Con International, Scott Bakula said that Bellisario was working on a script for a projected "Quantum Leap" feature film. In October 2017, Bellisario confirmed at the L.A. Comic Con that he has finished a script for a feature film.  NBC has also stated they have considered a potential relaunch of "Quantum Leap" for its upcoming Peacock streaming service, according to NBC's head of program planning and strategy, Jeff Bader.

In popular culture.

Adult Swim's "Robot Chicken" has parodied the show on at least two occasions, once showing the character of Sam Beckett leaping into a woman who appeared to be a sex worker. On another episode, a character is shown 'leaping' into other characters, and his reflection is not his own. This episode also features an opening theme similar to "Quantum Leap".  Seth McFarlane's "Family Guy" has referenced the show on at least three different episodes. In "The Father, the Son, and the Holy Fonz", Peter Griffin is shown going door-to-door as a Jehovah's witness and says that Jesus, "would travel from place to place putting things right that once went wrong, and hoping each time that his next leap would be the leap home"; then the show cuts away to an animated Jesus 'leaping' into a scene. In "The Kiss Seen Around the World", Al the hologram is shown entering a scene as he would on "Quantum Leap" and character Neil Goldman asks, "Al, why haven't I leaped?" In the episode "Back to the Pilot", Stewie says he learned the rules of time travel by watching the show.  On June 16, 2016, Scott Bakula made a brief reprise of his role as Sam Beckett on "The Late Show with Stephen Colbert". Colbert made a reference to an episode where Sam Beckett has leapt into the body of a 1950s New York cab driver, whose comment about investing in New York real estate is heard by a young Donald Trump. Using a handset to talk to Ziggy, Colbert leaps back as a hologram to help Sam Beckett attempt to change the future.  The show is referenced in "," when Scott Lang and James Rhodes try to explain time travel to Bruce Banner through the many times it's brought up in pop culture.  "Source Code", a 2011 science-fiction action thriller film, was directed by Duncan Jones. Jones said in reading its script that he was reminded of "Quantum Leap" and as a reference to the show, cast Bakula in a voice cameo role, including giving him one line of "Oh, boy" in the script.  Special episodes of "" ("") and "" (""), both series that feature Bakula as lead, have included Stockwell as a guest star to reunite the two actors from "Quantum Leap". Further, "Chasing Ghosts" was directed by James Whitmore Jr., who had directed a number of "Quantum Leap" episodes.

Quantum Leap is an American science-fiction television series created by Donald P. Bellisario, that originally aired on NBC for five seasons, from March 25, 1989, through May 5, 1993. It starred Scott Bakula as Dr. Sam Beckett, a physicist who leaps through spacetime during an experiment in time travel, by temporarily taking the place of other people to correct historical mistakes. Dean Stockwell co-stars as Admiral Al Calavicci, Sam's womanizing, cigar-smoking companion and best friend, who appears to him as a hologram.

Zurück in die Vergangenheit (Originaltitel: "Quantum Leap") ist eine US-amerikanische Science-Fiction-Fernsehserie, die von März 1989 bis Mai 1993 von NBC produziert wurde. Die von Donald P. Bellisario entwickelte und für die NBC produzierte Serie umfasst 5 Staffeln mit insgesamt 97 Episoden zu je ca. 45 Minuten. Die Titelmusik wurde von Mike Post komponiert.


Medications.

There are 8 FDA approved SNRIs in the United States, with venlafaxine being the first drug to be developed in 1993 and levomilnacipran being the latest drug to be developed in 2013. The drugs vary by their other medical uses, chemical structure, adverse effects, and efficacy.  Approval years for SNRIs:

History.

In 1952, iproniazid, an antimycobacterial agent, was discovered to have psychoactive properties while researched as a possible treatment for tuberculosis. Researchers noted that patients given iproniazid became cheerful, more optimistic, and more physically active. Soon after its development, iproniazid and related substances were shown to slow enzymatic breakdown of serotonin, dopamine, and norepinephrine via inhibition of the enzyme monoamine oxidase. For this reason, this class of drugs became known as monoamine oxidase inhibitors, or MAOIs. During this time development of distinctively different antidepressant agents was also researched. Imipramine became the first clinically useful tricyclic antidepressant (TCA). Imipramine was found to affect numerous neurotransmitter systems and to block the reuptake of norepinephrine and serotonin from the synapse, therefore increasing the levels of these neurotransmitters. Use of MAOIs and TCAs gave major advances in treatment of depression but their use was limited by unpleasant side effects and significant safety and toxicity issues.  Throughout the 1960s and 1970s, the catecholamine hypothesis of emotion and its relation to depression was of wide interest and that the decreased levels of certain neurotransmitters, such as norepinephrine, serotonin, and dopamine might play a role in the pathogenesis of depression. This led to the development of fluoxetine, the first SSRI. The improved safety and tolerability profile of the SSRIs in patients with MDD, compared with TCAs and MAOIs, represented yet another important advance in the treatment of depression.  Since the late 1980s, SSRIs have dominated the antidepressant drug market. Today, there is increased interest in antidepressant drugs with broader mechanisms of action that may offer improvements in efficacy and fewer adverse effects. In 1993, a new drug was introduced to the US market called venlafaxine, a serotonin-norepinephrine reuptake inhibitor. Venlafaxine was the first compound described in a new class of antidepressive substances called phenylethylamines. These substances are unrelated to TCA and other SSRIs. Venlafaxine blocks the neuronal reuptake of serotonin, noradrenaline, and, to a lesser extent, dopamine in the central nervous system. In contrast with several other antidepressant drugs, venlafaxine can induce a rapid onset of action mainly due to a subsequent norepinephrine reuptake inhibition. See timeline in figure 1.

Mechanism of action.

Monoamines are connected to the pathophysiology of depression. Symptoms may occur because concentrations of neurotransmitters, such as norepinephrine and serotonin, are insufficient, leading to downstream changes. Medications for depression affect the transmission of serotonin, norepinephrine, and dopamine. Older and more unselective antidepressants like TCAs and MAOIs inhibit the reuptake or metabolism of norepinephrine and serotonin in the brain, which results in higher concentrations of neurotransmitters. Antidepressants that have dual mechanisms of action inhibit the reuptake of both serotonin and norepinephrine and, in some cases, inhibit with weak effect the reuptake of dopamine. Antidepressants affect variable neuronal receptors like muscarinic-cholinergic, α- and α-adrenergic, and H-histaminergic receptors, and sodium channels in the cardiac muscle, leading to decreased cardiac conduction and cardiotoxicity {source needed}. Selectivity of antidepressant agents are based on the neurotransmitters that are thought to influence symptoms of depression. Drugs that selectively block the reuptake of serotonin and norepinephrine effectively treat depression and are better tolerated than TCAs. TCAs have comprehensive effects on various neurotransmitters receptors, which leads to lack of tolerability and increased risk of toxicity.

Tricyclic antidepressants.

TCAs were the first medications that had dual mechanism of action. The mechanism of action of tricyclic secondary amine antidepressants is only partly understood. TCAs have dual inhibition effects on norepinephrine reuptake transporters and serotonin reuptake transporters. Increased norepinephrine and serotonin concentrations are obtained by inhibiting both of these transporter proteins. TCAs have substantially more affinity for norepinephrine reuptake proteins than the SSRIs. This is because of a formation of secondary amine TCA metabolites.  In addition, the TCAs interact with adrenergic receptors. This interaction seems to be critical for increased availability of norepinephrine in or near the synaptic clefts. Actions of imipramine-like tricyclic antidepressants have complex, secondary adaptions to their initial and sustained actions as inhibitors of norepinephrine transport and variable blockade of serotonin transport.  Norepinephrine interacts with postsynaptic α and β adrenergic receptor subtypes and presynaptic α autoreceptors. The α receptors include presynaptic autoreceptors which limit the neurophysiological activity of noradrenergic neurons in the central nervous system. Formation of norepinephrine is reduced by autoreceptors through the rate-limiting enzyme tyrosine hydroxylase, an effect mediated by decreased cyclic AMP-mediated phosphorylation-activation of the enzyme. α receptors also cause decreased intracellular cyclic AMP expression which results in smooth muscle relaxation or decreased secretion.  TCAs activate a negative feedback mechanism through their effects on presynaptic receptors. One probable explanation for the effects on decreased neurotransmitter release is that, as the receptors activate, inhibition of neurotransmitter release occurs (including suppression of voltage-gated Ca currents and activation of G protein-coupled receptor-operated K currents). Repeated exposure of agents with this type of mechanism leads to inhibition of neurotransmitter release, but repeated administration of TCAs finally leads to decreased responses by α receptors. The desensitization of these responses may be due to increased exposure to endogenous norepinephrine or from the prolonged occupation of the norepinephrine transport mechanisms (via an allosteric effect). The adaptation allows the presynaptic synthesis and secretion of norepinephrine to return to, or even exceed, normal levels of norepinephrine in the synaptic clefts. Overall, inhibition of norepinephrine reuptake induced by TCAs leads to decreased rates of neuron firing (mediated through α autoreceptors), metabolic activity, and release of neurotransmitters.  TCAs do not block dopamine transport directly but might facilitate dopaminergic effects indirectly by inhibiting dopamine transport into noradrenergic terminals of the cerebral cortex. Because they affect so many different receptors, TCAs have adverse effects, poor tolerability, and an increased risk of toxicity.

Selective serotonin reuptake inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) selectively inhibit the reuptake of serotonin and are a widely used group of antidepressants. With increased receptor selectivity compared to TCAs, undesired effects such as poor tolerability are avoided. Serotonin is synthesized from an amino acid called -tryptophan. Active transport system regulates the uptake of tryptophan across the blood–brain barrier. Serotonergic pathways are classified into two main ways in the brain: the ascending projections from the medial and dorsal raphe and the descending projections from the caudal raphe into the spinal cord.

Selective norepinephrine reuptake inhibitors.

Noradrenergic neurons are located in two major regions in the brain. These regions are locus coeruleus and lateral tegmental. With administration of SNRIs, neuronal activity in locus coeruleus region is induced because of increased concentration of norepinephrine in the synaptic cleft. This results in activation of α adrenergic receptors, as discussed previously.  Assays have shown that SNRIs have insignificant penchant for mACh, α and α adrenergic, or H receptors.

Dual serotonin and norepinephrine reuptake inhibitors.

Agents with dual serotonin and norepinephrine reuptake inhibition (SNRIs) are sometimes called non-tricyclic serotonin and norepinephrine reuptake inhibitors. Clinical studies suggest that compounds that increase the concentration in the synaptic cleft of both norepinephrine and serotonin are more successful than single acting agents in the treatment of depression, but the data is not conclusive whether SNRIs are a more effective treatment option over SSRIs for depression. Dual reuptake inhibitors have low affinity at neuronal receptors of the other neurotransmitters, which have low adverse effects compared with the TCAs. Nontricyclic antidepressants have improved potency and onset action acceleration in antidepressant response than SSRIs alone, which give the impression that synergism is an efficient property in mediating antidepressant activity.  The non-tricyclic SNRIs have several important differences that are based on pharmacokinetics, metabolism to active metabolites, inhibition of CYP isoforms, effect of drug-drug interactions, and the half-life of the nontricyclic SNRIs.  Combination of mechanisms of action in a single active agent is an important development in psychopharmacology.

Structure activity relationship (SAR).

Aryloxypropanamine scaffold.

Several reuptake inhibitors contain an aryloxypropanamine scaffold. This structural motif has potential for high affinity binding to biogenic amine transports. Drugs containing an aryloxypropanamine scaffold have selectivity profile for norepinephrine and serotonin transporters that depends on the substitution pattern of the aryloxy ring. Selective NRIs contain a substituent in 2' position of the aryloxy ring but SSRIs contain a substituent in 4' position of the aryloxy ring. Atomoxetine, nisoxetine and reboxetine all have a substitution group in the 2' position and are selective NRIs while compounds that have a substitution group in the 4' position (like fluoxetine and paroxetine) are SSRIs. Duloxetine contains a phenyl group fused at the 2' and 3' positions, therefore it has dual selective norepinephrine and serotonin reuptake inhibitory effects and has similar potencies for the both transporters. The nature of the aromatic substituent also has a significant influence on the activity and selectivity of the compounds as inhibitors of the serotonin or the norepinephrine transporters.

Cycloalkanol ethylamine scaffold.

Venlafaxine and desvenlafaxine contain a cycloalkanol ethylamine scaffold. Increasing the electron-withdrawing nature of the aromatic ring provides a more potent inhibitory effect of norepinephrine uptake and improves the selectivity for norepinephrine over the serotonin transporter. Effects of chloro, methoxy and trifluoromethyl substituents in the aromatic ring of cycloalkanol ethylamine scaffold were tested. The results showed that the strongest electron-withdrawing "m"-trifluoromethyl analogue exhibited the most potent inhibitory effect of norepinephrine and the most selectivity over serotonin uptake. WY-46824, a piperazine-containing derivative, has shown norepinephrine and dopamine reuptake inhibition. Further synthesis and testing identified WAY-256805, a potent norepinephrine reuptake inhibitor that exhibited excellent selectivity and was efficacious in animal models of depression, pain, and thermoregulatory dysfunction.

Milnacipran.

Milnacipran is structurally different from other SNRIs. The SAR of milnacipran derivatives at transporter level is still largely unclear and is based on in vivo efficacy that was reported in 1987. "N"-methylation of milnacipran in substituent group R and R reduces the norepinephrine and serotonin activity. Researches on different secondary amides in substitution groups R and R showed that π electrons play an important role in the interaction between transporters and ligands. A phenyl group in substituent R showed effect on norepinephrine transporters. Substituent groups in R and R with allylic double bond showed significant improved effect on both norepinephrine and serotonin transporters. Studies show that introducing a 2-methyl group in substituent R, the potency at norepinephrine and serotonin transporters are almost abolished. Methyl groups in substituent groups R and R also abolish the potency at norepinephrine and serotonin transporters. Researchers found that replacing one of the ethyl groups of milnacipran with an allyl moiety increases the norepinephrine potency. The pharmacophore of milnacipran derivatives is still largely unclear.  The conformation of milnacipran is an important part of its pharmacophore. Changing the SAR in milnacipran changes the stereochemistry of the compound and affects the norepinephrine and serotonin concentration. Milnacipran is marketed as a racemic mixture. Effects of milnacipran reside in the (1"S",2"R")-isomer and substitution of the phenyl group in the (1"S",2"R")-isomer has negative impact on norepinephrine concentration. Milnacipran has low molecular weight and low lipophilicity. Because of these properties, milnacipran exhibits almost ideal pharmacokinetics in humans such as high bioavailability, low inter-subject variability, limited liver enzyme interaction, moderate tissue distribution and a reasonably long elimination half-life. Milnacipran's lack of drug-drug interactions via cytochrome P450 enzymes is thought to be an attractive feature because many of the central nervous system drugs are highly lipophilic and are mainly eliminated by liver enzymes.

Future development of SAR.

The application of an aryloxypropanamine scaffold has generated a number of potent MAOIs. Before the development of duloxetine, the exploration of aryloxypropanamine SAR resulted in the identification of fluoxetine and atomoxetine. The same motif can be found in reboxetine where it is constrained in a morpholine ring system. Some studies have been made where the oxygen in reboxetine is replaced by sulfur to give arylthiomethyl morpholine. Some of the arylthiomethyl morpholine derivatives maintain potent levels of serotonin and norepinephrine reuptake inhibition. Dual serotonin and norepinephrine reuptake inhibition resides in different enantiomers for arylthiomethyl morpholine scaffold. Possible drug candidates with dual serotonin and norepinephrine reuptake inhibitory activity have also been derived from piperazine, 3-amino-pyrrolidine and benzylamine templates.

Clinical trials.

Several studies have shown that antidepressant drugs which have combined serotonergic and noradrenergic activity are generally more effective than SSRIs, which act upon serotonin reuptake by itself. Serotonergic-noradrenergic antidepressant drugs may have a modest efficacy advantage compared to SSRIs in treating major depressive disorder (MDD), but are slightly less well tolerated. Further research is needed to examine the possible differences of efficacy in specific MDD sub-populations or for specific MDD symptoms, between these classes of antidepressant drugs.  Data from clinical trials have indicated that SNRIs might have pain relieving properties. Although the perception and transmission of pain stimuli in the central nervous system have not been fully elucidated, extensive data support a role for serotonin and norepinephrine in the modulation of pain. Findings from clinical trials in humans have shown these antidepressants can to reduce pain and functional impairment in central and neuropathic pain conditions. This property of SNRIs might be used to reduce doses of other pain relieving medication and lower the frequency of safety, limited efficacy and tolerability issues. Clinical research data have shown in patients with GAD that the SNRI duloxetine is significantly more effective than placebo in reducing pain-related symptoms of GAD, after short-term and long-term treatment. However, findings suggested that such symptoms of physical pain reoccur in relapse situations, which indicates a need for ongoing treatment in patients with GAD and concurrent painful physical symptoms.

Indications.

SNRIs have been tested for treatment of the following conditions:

Pharmacology.

Route of administration.

SNRIs are delivered orally, usually in the form of capsules or tablets. It is recommended to take SNRIs in the morning with breakfast, which does not affect drug levels, but may help with certain side effects. Norepinephrine has activating effects in the body and therefore can cause insomnia in some patients if taken at bedtime. SNRIs can also cause nausea, which is usually mild and goes away within a few weeks of treatment, but taking the medication with food can help alleviate this. The drugs themselves are usually a fine crystalline powder that diffuses into the body during digestion.

Dosage.

Dosages vary depending on the SNRI used due to varying potencies of the drug in question as well as multiple strengths for each drug.

Mode of action.

The condition for which SNRIs are mostly indicated, major depressive disorder, is thought to be mainly caused by decreased levels of serotonin and norepinephrine in the synaptic cleft, causing erratic signaling. Based on the monoamine hypothesis of depression, which asserts that decreased concentrations of monoamine neurotransmitters leads to depressive symptoms, the following relations were determined: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." SNRIs work by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine. This results in increased extracellular concentrations of serotonin and norepinephrine and, consequently, an increase in neurotransmission. Most SNRIs including venlafaxine, desvenlafaxine, and duloxetine, are several fold more selective for serotonin over norepinephrine, while milnacipran is three times more selective for norepinephrine than serotonin. Elevation of norepinephrine levels is thought to be necessary for an antidepressant to be effective against neuropathic pain, a property shared with the older tricyclic antidepressants (TCAs), but not with the SSRIs.  Recent studies have shown that depression may be linked to increased inflammatory response, thus attempts at finding an additional mechanism for SNRIs have been made. Studies have shown that SNRIs as well as SSRIs have significant anti-inflammatory action on microglia in addition to their effect on serotonin and norepinephrine levels. As such, it is possible that an additional mechanism of these drugs that acts in combination with the previously understood mechanism exist. The implication behind these findings suggests use of SNRIs as potential anti-inflammatories following brain injury or any other disease where swelling of the brain is an issue. However, regardless of the mechanism, the efficacy of these drugs in treating the diseases for which they have been indicated has been proven, both clinically and in practice.

Pharmacodynamics.

Most SNRIs function alongside primary metabolites and secondary metabolites in order to inhibit reuptake of serotonin, norepinepherine, and marginal amounts of dopamine. For example, venlafaxine works alongside its primary metabolite "O"-desmethylvenlafaxine to strongly inhibit serotonin and norepinephrine reuptake in the brain. The evidence also suggests that dopamine and norepinepherine behave in a co-transportational manner, due to the inactivation of dopamine by norepinephrine reuptake in the frontal cortex, an area of the brain largely lacking in dopamine transporters. This effect of SNRIs results in increased dopamine neurotransmission, in addition to the increases in serotonin and norepinephrine activity. Furthermore, because SNRIs are extremely selective, they have no measurable effects on other, unintended receptors, in contrast to monoamine oxidase inhibition. Pharmaceutical tests have determined that use of both SNRIs or SSRIs can generate significant anti-inflammatory action on microglia, as well.

Pharmacokinetics.

The half-life of venlafaxine is about 5 hours, and with once-daily dosing, steady-state concentration is achieved after about 3 days, though its active metabolite desvenlafaxine lasts longer. The half-life of desvenlafaxine is about 11 hours, and steady-state concentrations are achieved after 4 to 5 days. The half-life of duloxetine is about 12 hours (range: 8–17 hours), and steady-state is achieved after about 3 days. Milnacipran has a half-life of about 6 to 8 hours, and steady-state levels are reached within 36 to 48 hours.

Contraindications.

SNRIs are contraindicated in patients taking MAOIs within the last two weeks due to the increased risk of serotonin syndrome, which can be life-threatening. Other drugs and substances that should be avoided due to increased risk of serotonin syndrome when combined with an SNRI include: other anti-depressants, anti-convulsants, analgesics, antiemetic agents, anti-migraine medications, methylene blue, linezolid, Lithium, St. John's worts, ecstasy, and LSD. Signs and symptoms of serotonin syndrome include: hyperthermia, rigidity, myoclonus, autonomic instability with fluctuating vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.  Due to the effects of increased norepinephrine levels and, therefore, higher noradrenergic activity, pre-existing hypertension should be controlled before treatment with SNRIs and blood pressure periodically monitored throughout treatment. Duloxetine has also been associated with cases of liver failure and should not be prescribed to patients with chronic alcohol use or liver disease. Studies have found that Duloxetine can increase liver function tests three times above their upper normal limit. Patients suffering from coronary artery disease should caution the use of SNRIs. Furthermore, due to some SNRIs' actions on obesity, patients with major eating disorders such as anorexia nervosa or bulimia should not be prescribed SNRIs. Duloxetine and milnacipran are also contraindicated in patients with uncontrolled narrow-angle glaucoma, as they have been shown to increase incidence of mydriasis.

Side effects.

Because the SNRIs and SSRIs act in similar ways to elevate serotonin levels, they share many side effects, though to varying degrees. The most common side effects include nausea/vomiting, sweating, loss of appetite, dizziness, headache, increase in suicidal thoughts, and sexual dysfunction. Elevation of norepinephrine levels can sometimes cause anxiety, mildly elevated pulse, and elevated blood pressure. However, norepinephrine-selective antidepressants, such as reboxetine and desipramine, have successfully treated anxiety disorders. People at risk for hypertension and heart disease should monitor their blood pressure. The side effects of upset stomach may be decreased by taking SNRIs with food.

Sexual Dysfunction.

SNRIs, similarly to SSRIs, can cause several types of sexual dysfunction, such as erectile dysfunction, decreased libido, sexual anhedonia, and anorgasmia. The two common sexual side effects are diminished interest in sex (libido) and difficulty reaching climax (anorgasmia), which are usually somewhat milder with SNRIs compared to SSRIs. To manage sexual dysfunction, studies have shown that switching to or augmenting with bupropion or adding a PDE5 Inhibitor have decreased symptoms of sexual dysfunction. Studies have shown that PDE5 Inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra), have sometimes been helpful to decrease the sexual dysfunction, including erectile dysfunction, although they have been shown to be more effective in men than women.

Serotonin Syndrome.

A serious, but rare, side effect of SNRIs is serotonin syndrome, which is caused by an excess of serotonin in the body. Serotonin syndrome can be caused by taking multiple serotonergic drugs, such as SSRIs or SNRIs. Other drugs that contribute to serotonin syndrome include MAO inhibitors, linezolid, tedizolid, methylene blue, procarbazine, amphetamines, clomipramine, and more. Early symptoms of serotonin syndrome may include nausea, vomiting, diarrhea, sweating, agitation, confusion, muscle rigidity, dilated pupils, hyperthermia, rigidity, and goose bumps. More severe symptoms include fever, seizures, irregular heartbeat, delirium, and coma. If signs or symptoms arise, discontinue treatment with serotonergic agents immediately. It is recommended to washout 4 to 5 half-lives of the serotonergic agent before using an MAO inhibitor.

Bleeding.

Some studies suggest there are risks of upper gastrointestinal bleeding, especially venlafaxine, due to impairment of platelet aggregation and depletion of platelet serotonin levels. Similarly to SSRIs, SNRIs may interact with anticoagulants, like warfarin. Currently, there is more evidence of SSRIs having higher risk of bleeding than SNRIs. Studies have suggested caution when using SNRIs or SSRIs with high doses of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or naproxen due to an increased risk of upper GI bleeding.

Precautions.

Starting an SNRI regimen.

Due to the extreme changes in noradrenergic activity produced from norepinephrine and serotonin reuptake inhibition, patients that are just starting an SNRI regimen are usually given lower doses than their expected final dosing to allow the body to acclimate to the drug's effects. As the patient continues along at low doses without any side-effects, the dose is incrementally increased until the patient sees improvement in symptoms without detrimental side-effects. Effects may be seen in 1 to 2 weeks, with full efficacy occurring in 4 to 6 weeks.

Discontinuation syndrome.

As with SSRIs, the abrupt discontinuation of an SNRI usually leads to withdrawal, or "discontinuation syndrome", which could include states of anxiety and other symptoms. Therefore, it is recommended that users seeking to discontinue an SNRI slowly taper the dose under the supervision of a professional. Discontinuation syndrome has been reported to be markedly worse for venlafaxine when compared to other SNRIs. As such, as tramadol is related to venlafaxine, the same conditions apply. This is likely due to venlafaxine's relatively short half-life and therefore rapid clearance upon discontinuation. In some cases, switching from venlafaxine to fluoxetine, a long-acting SSRI, and then tapering off fluoxetine, may be recommended to reduce discontinuation symptoms. Signs and symptoms of withdrawal from abrupt cessation of an SNRI include dizziness, anxiety, insomnia, nausea, sweating, and flu-like symptoms, such as lethargy and malaise.

Overdose.

Causes.

Overdosing on SNRIs can be caused by either drug combinations or excessive amounts of the drug itself. Venlafaxine is marginally more toxic in overdose than duloxetine or the SSRIs. Risk of overdose is increased in patients taking multiple serotonergic agents or interacting agents.

Symptoms.

Symptoms of SNRI overdose, whether it be a mixed drug interaction or the drug alone, vary in intensity and incidence based on the amount of medicine taken and the individuals sensitivity to SNRI treatment. Possible symptoms may include:

Management.

Overdose is usually treated symptomatically, especially in the case of serotonin syndrome, which requires treatment with cyproheptadine and temperature control based on the progression of the serotonin toxicity. Patients are often monitored for vitals and airways cleared to ensure that they are receiving adequate levels of oxygen. Another option is to use activated carbon in the GI tract in order to absorb excess neurotransmitter. It is important to consider drug interactions when dealing with overdose patients, as separate symptoms can arise.

Comparison to SSRIs.

Because SNRIs were developed more recently than SSRIs, there are relatively few of them. However, the SNRIs are among the most widely used antidepressants today. In 2009, Cymbalta and Effexor were the 11th- and 12th-most-prescribed branded drugs in the United States, respectively. This translates to the 2nd- and 3rd-most-common antidepressants, behind Lexapro (escitalopram), an SSRI. In some studies, SNRIs demonstrated slightly higher antidepressant efficacy than the SSRIs (response rates 63.6% versus 59.3%). However, in one study escitalopram had a superior efficacy profile to venlafaxine.

Special populations.

Pregnancy.

Currently, no antidepressants are FDA approved during pregnancy. All SSRIs and SNRIs are Category C, except paroxetine, which is Category D since it has shown association with congenital heart disorders. Use of antidepressants during pregnancy may result in fetus abnormalities affecting functional development of the brain and behavior. Untreated depression may also affect birth outcomes, so it is recommended to discuss options with a provider to weigh the risks and benefits.

Pediatrics.

SSRIs and SNRIs have been shown to be effective in treating major depressive disorder and anxiety in pediatric populations. However, there is a risk of increased suicidality in pediatric populations for treatment of major depressive disorder, especially with venlafaxine. Fluoxetine is the only antidepressant that is approved for child/adolescent major depressive disorder.

Geriatrics.

Most antidepressants, including SNRIs, are safe and effective in the geriatric population. Decisions are often based on co-morbid conditions, drug interactions, and patient tolerance. Due to differences in body composition and metabolism, starting doses are often half that of the recommended dose for younger adults.

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant drugs that treat major depressive disorder (MDD), anxiety disorders, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act upon serotonin only.

Serotonin-Noradrenalin-Wiederaufnahmehemmer (SSNRI = "Selective Serotonin-Noradrenalin-Reuptake-Inhibitor"; deutsch auch Selektive Serotonin-Noradrenalin-Reuptake-Hemmer) sind Arzneistoffe, die vorwiegend als Antidepressiva eingesetzt werden. Die SSNRI (oft nur als "SNRI" bezeichnet) entfalten ihre Wirkung an den Serotonin- und Noradrenalin-Transportern. Der erste Vertreter dieser Gruppe war 1993 der Wirkstoff Venlafaxin.


Overview.

The term was popularized by Naomi Klein. In her 2007 book "The Shock Doctrine", she argues that neoliberal free market policies (as advocated by the economist Milton Friedman) have risen to prominence in some developed countries because of a deliberate strategy of "shock therapy". Johan Norberg of the Cato Institute criticized the book, saying that the concept of shock therapy is falsely attributed to Friedman. According to Norberg, Friedman's quote ("Only a crisis—actual or perceived—produces real change") is taken out of context and misinterpreted.  The economist Jeffrey Sachs (sometimes credited with coining the term) says he never picked the term "shock therapy", does not much like it, and asserts that the term "was something that was overlaid by journalism and public discussion" and that the term "sounds a lot more painful in a way than what it is". Sachs' ideas on what has been referred by non-economists as "shock therapy" were based on studying historic periods of monetary and economic crisis and noting that a decisive stroke could end monetary chaos, often in a day.  The first instance of shock therapy was the neoliberal reforms of Chile in 1975, carried out after the military coup by Augusto Pinochet. The reforms were based on the

History.

West Germany 1948.

Though the term "shock therapy" only came into existence after Bolivia's actions in 1985, both Gonzalo Sánchez de Lozada (the architect of the policy in Bolivia) and Jeffrey Sachs (its economic architect) were heavily influenced by West Germany's reforms in 1948.

Background.

Germany ended the European Theatre of World War II with its unconditional surrender on the 8 May 1945. It faced war damage to its economy and the problems of mass migration due to the expulsion of ethnic Germans from areas east of the Oder-Neisse Line.  April 1945 to July 1947 saw the Allied occupation of Germany implement Joint Chiefs of Staff directive 1067 (JCS 1067). This directive aimed to transfer Germany's economy from one centred on heavy industry to a pastoral one to prevent Germany from having the capacity for war. Civilian industries that might have military potential, which in the modern era of "total war" included virtually all, were severely restricted. The restriction of the latter was set to Germany's "approved peacetime needs", which were set on the average European standard. To achieve this, each type of industry was subsequently reviewed to see how many factories Germany required under these minimum level of industry requirements. In May 1946, the first plan stated that German heavy industry must be lowered to 50% of its 1938 levels by the destruction of

Economic reforms.

In spring of 1948, the Allies decided to reform the currency. In preparation for this, a new central bank system was established in West Germany with independent Land Central Banks and the Bank deutscher Lander with headquarters in Frankfurt am Main.  Currency reform took effect on June 20, 1948, through the introduction of the Deutsche Mark to replace the Reichsmark and by transferring to the Bank deutscher Lander the sole right to print money. Each person received a per capita allowance of 60 DM, payable in two installments (40 DM and 20 DM) and business quota of 60 DM per employee.  Under

Results.

In the short term, the currency reforms and abolition of price controls helped end hyperinflation. The new currency enjoyed considerable confidence and was accepted by the public as a medium of payment. The currency reforms had ensured that money was once more scarce, and the relaxation of price controls created incentives for production, sales and earning this money. The removal of price controls also meant shops filled up with goods again, which was a huge psychological factor in the adoption of the new currency.  In the long term, these reforms helped set the stage for the Wirtschaftswunder (German for economic miracle) in the 1950s.

Chile 1975.

Chile's reforms under the government of Augusto Pinochet are held as the origin of neoliberal shock therapy.

Economic reforms.

The government welcomed foreign investment and eliminated protectionist trade barriers, forcing Chilean businesses to compete with imports on an equal footing, or else go out of business. The main copper company, Codelco, remained in government hands due the nationalization of copper completed by Salvador Allende, however, private companies were allowed to explore and develop new mines. Copper resources were, however, declared "inalienable" by the 1980 Constitution.  In the short term, the reforms stabilised the economy.  In the long term, Chile has had higher GDP growth than its neighbouring countries, but also high gini index, expressed in a noticeable inequality.

Bolivia 1985.

The term "shock therapy" originates from Bolivia's tackling of hyper-inflation in 1985, and was thought to have been coined by the media. On 29 August, just three weeks after the election of Víctor Paz Estenssoro as President, and the appointment of Gonzalo Sánchez de Lozada, the architect of shock therapy, as Planning Minister, Decree 21060 was passed. This decree tackled all aspects of the Bolivian economy and ended the hyper-inflation.

Background.

Between 1979 and 1982, Bolivia was ruled by a series of coups, counter-coups, and caretaker governments, including the notorious dictatorship of Luis García Meza Tejada. This period of political instability set the stage for the hyperinflation that later crippled the country. In October 1982, the military convened a Congress elected in 1980 to lead choose a new Chief Executive. The country elected Hernán Siles Zuazo, under whose term the

Prelude to Decree 21060.

Decree 21060 was the famous decree that covered all aspects of the Bolivian economy, later referred to as shock therapy. In the run-up to the decree, Gonzalo Sánchez de Lozada recalls what the new government set out to do:  In the three weeks between the inauguration of the President and decree 21060,

Decree 21060.

Decree 21060

Results.

In the short term, the decree smothered hyperinflation. Within a few months, inflation had dropped to between 10 and 20 percent. The crash of the tin market in October of the same year and the reforms led to an estimated unemployment rate of 21.5 percent by 1987 (the unemployment rate had risen steadily from 5.5 percent in 1978 to 10.9 percent in 1982, 15.5 percent in 1984, and 20 percent in 1986).

Post-Communist states.

The next important chapter in the history of shock therapy was the collapse of communism in Europe in 1989. This left many post-communist states in central and eastern Europe with centralised authoritarian economies that had to transition to decentralised, market-orientated capitalist economies.  Inspired by Bolivia's example, and advised by institutions like the International Monetary Fund and individuals like Jeffrey Sachs, many countries chose shock therapy to shake off the economic lethargy of the communist era and transition to the capitalist systems. These transitions provide an interesting and important view into shock therapy and its consequences, especially when contrasted with China, which began a gradualist transition (the opposite of the shock therapy approach) in 1978 under Deng Xiaoping.  Advocates of shock therapy view Poland as the success story of shock therapy in the post-communist states and point out that shock therapy was not applied appropriately in Russia, while critics point out that Poland's reforms were the most gradualist of all the countries and compare China's reforms with those of Russia and their vastly different effects.

Background.

After the failure of the Communist government in the elections of June 4, 1989, it became clear that the previous regime was no longer legitimate. The unofficial talks at Magdalenka and then the Polish Round Table talks of 1989 allowed for a peaceful transition of power to the democratically elected government.  The economic situation was that inflation was high, peaking at around 600%, and the majority of state-owned monopolies and holdings were largely ineffective and completely obsolete in terms of technology. Although there was practically no unemployment

Balcerowicz Plan.

On October 6 the program was presented on public television and in December the Sejm passed a

Results.

In the short term, the reforms smothered the building hyperinflation before it reached high levels, ended food shortages, restored goods on the shelves of shops and halved the absence of employees in the work place. However, the reforms also caused many state companies to close at once, leaving their workers unemployed, and government statistics show this change as unemployment rose from 0.3% in January 1990 (just after the reforms) to 6.5% by the end of that year, and a shrinking in the GDP for the next two consecutive years by 9.78% in the first and 7.02% (see main article).  In the long term, the reforms paved the way for economic recovery, with the GDP growing steadily to

Applications.

This section records all known applications of shock therapy in the world not mentioned under the history section above.

New Zealand.

The economic reforms of New Zealand's 1984 Labour government, collectively known as Rogernomics (after New Zealand Finance Minister Roger Douglas), constitute an example of shock therapy. In this case, the previous economic direction and management of Rob Muldoon

Post-Soviet.

Since the USSR's dissolution, the post-Soviet states faced many problems. Poverty in the region had increased more than tenfold. The economic crisis that struck all post-Soviet countries in the 1990s was twice as intense as the Great Depression in the countries of Western Europe and the United States in the 1930s.  However, it has not been established whether these adverse outcomes were due to the general collapse of the Soviet economy

Poland.

Poland has been cited by some as an example of the successful use of shock therapy, though this is disputed. When economic liberalism came to this nation, the government took Sachs' advice and immediately withdrew regulations, price controls and subsidies to state-owned industries. However, with respect to the privatization of the state sector (which may or may not be considered as part of shock therapy depending on the definition being used) the change was much more gradualist.

Theory.

This section presents the various theories that are used to explain shock therapy and its effects.

Hyperinflation.

Jeffrey Sachs first proposed shock therapy when he noticed that most periods of hyperinflation had been ended in a decisive stroke, often in a day. Therefore, it is important to look at the theoretical basis for hyperinflation to understand why Sachs noticed shock therapy proved so successful in fighting it.  There are two main models used to explain hyperinflation, the "confidence model" and the "monetary model". Hyperinflations see a rapid increase in the money supply and the velocity of money. Either one, or both of these together, is the root cause of hyperinflation and in both models, one follows from the other.  In the "confidence model", some event, or series of events, such as defeats in battle, or a run on stocks of the specie that back a currency, removes the belief that the authority issuing the money will remain solvent—whether a bank or a government. Because people do not want to hold notes that may become valueless, they want to spend them in preference to holding notes that will lose value. Sellers, realizing that there is a higher risk for the currency, demand a greater and greater premium over the original value. War is one commonly cited cause of crisis of confidence, particularly losing in a war, as occurred during Napoleonic Vienna, and capital flight, sometimes because of "contagion"

Shock therapy as an artificial economic shock.

A shock in economics is defined as an unexpected or unpredictable event that affects an economy, either positively or negatively. Recessions are often modelled as negative economic shocks in which the current state of the economy is untenable and the economy tries to restore itself to a new equilibrium position. In the short-run, as the economy adjusts to the shock but before it reaches the new equilibrium, the shock often causes productivity to fall, unemployment rise, and closure of firms that are now non-viable in the new environment. The new environment enables new kinds of businesses and people must learn new skills and exploit new opportunities to achieve long-run equilibrium.  Shock therapy can be largely understood by thinking of it as an artificial shock imposed by government policies. Neoclassical theory provides a very useful tool in trying to describe an artificial shock theoretically, in that neoclassical theory provides an idealised view of an economy based on certain assumptions, most of which are made true through market institutions (often but not necessarily provided by the government), law, culture or historical practise, and is very useful in explaining most situations (especially in modern Westernised economies). Even when some of the assumptions required for neoclassical theory are not in place resulting in an imperfect market and the results of neoclassical theory becoming distorted or failing, comparing the result with neoclassical theory can prove useful. Other, slightly different formulations of economic thought strive to describe shocks, the most important of which is economic liberalism.

Neoclassical shocks.

In neoclassical theory, large negative shocks cause unemployment in the short run, and the larger the shock, the larger the unemployment. As a result, large shocks can lead to grave social problems, political unrest and, in the worst cases revolution. However, the market is already adjusting itself to return to the new equilibrium, causing job creation and opportunities. If there is no interference to prevent the markets adjusting to the new equilibrium, the markets immediately correct themselves with new firms

Imperfect market shocks.

The most important type of nearly neoclassical shock is due to market failure and imperfect markets. Sudden free market liberalisation in the absence of free market institutions (as was the case in post-Communist states) or in which a Western-style economy is unnecessarily liberalised (e.g. cutting police budgets, removing regulation) are both examples of imperfect market shocks.  The nature of the imperfect market shock depends on what assumption of the perfect market is voided. The most important assumption for all markets is the idea of property rights. The free market doesn't just depend on the exchange of commodities, but on the rights to use them in particular ways for particular amounts of time. Markets are institutions that organize the exchange of control of commodities, where the nature of the control is defined by the property rights attached to the commodities. Property rights are the most important because they can have the most dramatic effect on the results, and are thought to be behind the most important causes of market failure.  Another important assumption is perfect competition, which

In economics, shock therapy is the sudden release of price and currency controls (economic liberalization), withdrawal of state subsidies, and immediate trade liberalization within a country, usually also including large-scale privatization of previously public-owned assets.

Als Schocktherapie wird eine Wirtschaftspolitik in denjenigen Staaten bezeichnet, die nach dem Zusammenbruch des Realsozialismus von Zentralverwaltungswirtschaften in kürzester Zeit zu Marktwirtschaften umgebaut wurden, den Transformationsökonomien. Insbesondere wird der Begriff zum Umbau der polnischen Wirtschaft seit der Wende verwendet. Nicht zu verwechseln ist die Schocktherapie mit der "Schock-Strategie", einer von Naomi Klein geprägten These, der zufolge Schocks ausgenutzt werden, um wirtschaftspolitische Reformen gegen den Willen der Mehrheit der Bevölkerung durchzusetzen.


Actions.

King Mob appreciated pop culture and distributed its ideas through various posters and through its publication "King Mob Echo", which provoked reaction by celebrating killers like Jack the Ripper, Mary Bell and John Christie. One flyer in particular celebrated Valerie Solanas' 1968 shooting of Andy Warhol and included a hit-list of Yoko Ono, Mick Jagger, Bob Dylan, Richard Hamilton, Mario Amaya (who was also shot by Solanas), David Hockney, Mary Quant, Twiggy, Marianne Faithfull and the "IT" editor Barry Miles.  The King Mob group allegedly planned a series of audacious actions, including blowing up a waterfall in the Lake District, painting the poet Wordsworth's house with the words "Coleridge Lives", and hanging peacocks in Holland Park, London. However, none of the aforementioned plans were executed. An action that was carried out, inspired by the New York-based Black Mask's "mill-in at Macy's", involved King Mob appearing at the Selfridges store in London, with one member, dressed as Father Christmas, attempting to distribute all of the store's toys to children. Police subsequently forced the children to return the toys. This action involved Malcolm McLaren who reputedly applied the group's situationist ideas in the promotion of the Sex Pistols.  King Mob was also responsible for attacks on art galleries and for organising a battle between local skinheads (whom they considered to be "the working class avant-garde") and greasers in central London.

Graffiti.

Graffiti attributed to King Mob was observed in many places particularly in the Notting Hill area, including, ""I don't believe in nothing - I feel like they ought to burn down the world - just let it burn down baby.""  The most celebrated graffiti attributed to King Mob was the slogan which was painted along a half-mile section of the wall beside the tube (railway) commuter route into London between Ladbroke Grove and Westbourne Park tube stations in west London:

References in popular culture.

"King Mob's Ape Mask" can be seen in the background of the comic book "Watchmen", written by Alan Moore. It is in what appears to be a trophy room of the Minutemen, noticeable during the infamous scene where The Comedian tries to rape the original Silk Specter.  A protagonist in the comic book series "The Invisibles" (authored by Grant Morrison) is codenamed "King Mob". The Invisibles is organized anti-hierarchically, and is dedicated to defeating a global conspiracy which deceives and preys upon the world's population. The character "King Mob" describes himself as an anarchist.  Graffiti referencing Grant Morrison's King Mob and The Invisibles appears in season 2 episode 7 of Stranger Things.  King Mob was the name of a punk band of which writer and Neoist anti-artist Stewart Home was once a member.

King Mob was an English radical group based in London during the late 1960s/early 1970s. It was a cultural mutation of the Situationists and the anarchist group UAW/MF. It sought to emphasise the cultural anarchy and disorder being ignored in Britain, with the ultimate aim of promoting proletarian revolution. It derived its name from Christopher Hibbert's 1958 book on the Gordon Riots of June 1780, in which rioters daubed the slogan "His Majesty King Mob" on the walls of Newgate Prison, after gutting the building.

King Mob war eine radikale aktionistische Londoner Künstlergruppe. Die britische Sektion der Situationistischen Internationalen wurde 1967 wegen ihrer Verbindungen zur anarchistischen New Yorker Künstlergruppe Up Against The Wall Motherfuckers ausgeschlossen, ihre Mitglieder gründeten King Mob. Der Name leitet sich von der Parole "His Majesty King Mob" ab, die von Beteiligten an den "Gordon Riots", einem protestantischen Aufruhr gegen die Gleichberechtigung der Katholiken Ende des 18. Jahrhunderts an die Wände des Londoner Newgate Gefängnisses geschmiert wurde. Der Name ist mit „König Pöbel“ zu übersetzen und drückt die antistaatlichen und anarchistischen Tendenzen der Gruppe aus.


Name.

The name "Muʿtazili" is derived from the reflexive stem VIII ("iftaʿala") of the triconsonantal root ع-ز-ل "separate, segregate", as in "iʿtazala" "to separate (oneself); to withdraw from".  The name is derived from the founder's "withdrawal" from the study circle of Hasan of Basra over a theological disagreement: Wāṣil ibn ʿAṭā' asked about the legal state of a sinner: is a person who has committed a serious sin a believer or an unbeliever? Hasan answered the person remains a Muslim. Wasil dissented, suggesting that a sinner was neither a believer nor an unbeliever and withdrew from the study circle. Others followed to form a new circle, including ʿAmr ibn ʿUbayd. Hasan's remark, "Wāṣil has withdrawn from us", is said to be the origin of the movement's name.  The group later referred to themselves as "Ahl al-Tawḥīd wa l-ʿAdl" (, "people of monotheism and justice", and the name "muʿtazili" was first used by its opponents.  The verb "iʿtizal" is also used to designate a neutral party in a dispute (as in "withdrawing" from a dispute between two factions). According to the "Encyclopædia Britannica", "The name [Mutazilah] first appears in early Islāmic history in the dispute over ʿAlī's leadership of the Muslim community after the murder of the third caliph, ʿUthmān (656). Those who would neither condemn nor sanction ʿAlī or his opponents but took a middle position were termed the Muʿtazilah." Nallino (1916) argued that the theological Mu'tazilism of Wasil and his successors was merely a continuation of this initial political Mu'tazilism.

History.

Origin.

According to Sunni sources, Muʿtazili theology originated in the eighth century in Basra (now in Iraq) when Wāṣil ibn ʿAṭā' (d. 131 AH/748 AD) left the teaching lessons of Hasan al-Basri after a theological dispute regarding the issue of "al-Manzilah bayna al-Manzilatayn" ("a position between two positions"). Though Muʿtazilis later relied on logic and different aspects of early Islamic philosophy, ancient Greek philosophy, and Indian philosophy, the basics of Islam were their starting point and ultimate reference. The accusations leveled against them by rival schools of theology that they gave absolute authority to extra-Islamic paradigms reflect more the fierce polemics between various schools of theology than any objective reality. For instance, Muʿtazilis adopted unanimously the doctrine of creation "ex nihilo", contrary to certain Muslim philosophers who, with the exception of al-Kindi, believed in the eternity of the world in some form or another.  Scholar Daniel Brown describes the Muʿtazili as "the later "ahl al-kalām"", suggesting the "ahl al-kalām" were forerunners of the Muʿtazili. The "ahl al-kalām" are remembered in Islamic history as opponents of Al-Shafi‘i and his principle that the final authority of Islam was the hadith of Muhammad, so that even the Qur'an was "to be interpreted in the light of [the hadith], and not vice versa." "Ahl al-kalām" argued to the contrary, that the book of God was an explanation of everything (), and that verses in the Qur'an ordering Muslims to obey the Messenger meant that Muslims should obey the Qur'an, which God had revealed through Muhammad.

Historical development.

Abu al-Hudhayl al-'Allaf (d. 235 AH/849 AD), who came a couple of generations after Wāṣil ibn ʿAtāʾ (واصل بن عطاء) and ʿAmr ibn ʿUbayd, is considered the theologian who systematized and formalized Muʿtazilism in Basra. Another branch of the school found a home in Baghdad under the direction of Bishr ibn al-Mu'tamir (d. 210 AH/825 AD); the instigators thought it was the Caliph's own scheme: under Ma`mun the Great (813-833), "Muʿtazilism became the established faith.  The first Caliph however to adopt the principles of the Mu’tazilite doctrine was the Umayyad Caliph Al-Walid II.  The Muʿtazilites maintained man's free will, as did the Qadarites of the later Omayyad period. The Muʿtazilites also maintained that justice and reason must form the foundation of the action God takes toward men. Both of these doctrines were repudiated by the later orthodox school of the Ashʿarites."  The persecution campaign, nonetheless, cost them their theology and generally, the sympathy of the Muslim masses. As the number of Muslims increased throughout the Islamic empire, and in reaction to the excesses of this newly imposed rationalism, theologians began to lose ground. The problem was exacerbated by the Mihna, the inquisition launched under the Abbasid caliph al-Ma'mun (d. 218 AH/833 AD). Ahmad ibn Hanbal, the Sunni jurist and founder of the Hanbali school of thought was a victim of Ma'mun's Mihna. Due to his rejection of Ma'mun's demand to accept and propagate the Muʿtazila creed, ibn Hanbal was imprisoned and tortured by the Abbasid rulers. Under Caliph al-Mutawakkil (847-861), "who sought to reestablish the traditional Moslem faith" (intentionally wanted to restore his legitimacy due to backlash towards Ahmad Ibn Hanbal's persecution under previous Caliphs), Muʿtazilite doctrines were repudiated; their professors persecuted; Shias, Christians and Jews were also persecuted."

Muʿtazilism today.

Today, Mu‘tazilism persists mainly in the Maghreb among those who call themselves the "Wasiliyah", referencing Wasil ibn ‘Ata the reputed founder of Mu‘tazila, the movement uses the mantle of the Mu‘tazila primarily as an identity marker.  Sheikh Muhammad Abduh (1849-1905) was one of the key founding figures of Islamic Modernism that contributed to a revival of Muʿtazilite thought, although he does not seem to have called himself a Muʿtazilite. After he was appointed Grand Mufti of Egypt in 1899, he attempted to adapt Islam to the modern times and to introduce changes in its teaching, in particular at Al-Azhar University. His reforms met with much opposition from the traditional establishment but, even though his immediate successors, such as Rashid Rida (1865-1935), did not follow in his steps, he was a source of inspiration for later modernist and reformist scholars and philosophers such as Fazlur Rahman (1919-1988), Farid Esack (born 1959), and in particular Harun Nasution (1919-1998) and Nasr Abu Zayd (1943-2010), who openly espoused Muʿtazilite views.  The Association for the Renaissance of Mu'tazilite Islam (, ARIM) was founded in France in February 2017.

Beliefs.

The Five Principles.

According to a "leading Muʿtazilite authority" of the end of the ninth century (Al-Khayyat), and "clearly enunciated for the first time by Abu al-Hudhayl", five basic tenets make up the Mu'tazilite creed:

Monotheism.

All Muslim schools of theology faced the dilemma of affirming divine transcendence and divine attributes, without falling into anthropomorphism on the one hand or emptying scriptural references to those attributes of all concrete meaning.  The doctrine of Tawhīd, in the words of the prominent Muʿtazili scholar Chief Justice Qadi Abd al-Jabbar (d. 415 AH/1025 AD), is: the knowledge that God, being unique, has attributes that no creature shares with him. This is explained by the fact that you know that the world has a creator who created it and that: he existed eternally in the past and he cannot perish while we exist after being non-existent and we can perish. And you know that he was and is eternally all-powerful and that impotence is not possible for him. And you know that he is omniscient of the past and present and that ignorance is not possible for him. And you know that he knows everything that was, everything that is, and how things that are not would be if they were. And you know that he is eternally in the past and future living, and that calamities and pain are not possible for him. And you know that he sees visible things, and perceives perceptibles, and that he does not have need of sense organs. And you know that he is eternally past and in future sufficient and it is not possible for him to be in need. And you know that he is not like physical bodies, and that it is not possible for him to get up or down, move about, change, be composite, have a form, limbs and body members. And you know that he is not like the accidents of motion, rest, color, food or smells. And you know that he is One throughout eternity and there is no second beside him, and that everything other than he is contingent, made, dependent, structured, and governed by someone/thing else. Thus, if you know all of that you know the oneness of God.

Divine justice.

Facing the problem of existence of evil in the world, the Muʿtazilis pointed at the free will of human beings, so that evil was defined as something that stems from the errors in human acts. God does nothing ultimately evil, and he demands not from any human to perform any evil act. If man's evil acts had been from the will of God, then punishment would have been meaningless, as man performed the will of God no matter what he did. Muʿtazilis did not deny the existence of suffering that goes beyond human abuse and misuse of their free will granted to them by God. In order to explain this type of "apparent" evil, Muʿtazilis relied on the Islamic doctrine of "taklif" — "God does not order/give the soul of any of his creation, that which is beyond its capacity." [Qur'an 2:286] This entailed the existence of an "act of god" to serve a greater good, or the existence of evil acts to prevent a far greater evil. In conclusion, it comprised life is an ultimate "fair test" of coherent and rational choices, having a supremely just accountability in one's current state, as well as the hereafter.  Humans are required to have belief, "iman", secure faith and conviction in and about God, and do good works, "amal saleh", to have "iman" reflected in their moral choices, deeds, and relationship with God, fellow humans, and all of the creation in this world. If everyone is healthy and wealthy, then there will be no meaning for the obligations imposed on humans to, for example, be generous, help the needy, and have compassion for the deprived and trivialized. The inequalities in human fortunes and the calamities that befell them are, thus, an integral part of the test of life. Everyone is being tested. The powerful, the rich, and the healthy are required to use all their powers and privileges to help those who suffer and to alleviate their suffering. In the Qiyamah (Judgment Day), they will be questioned about their response to Divine blessings and bounties they enjoyed in their lives. The less fortunate are required to patiently persevere and are promised a compensation for their suffering that, as the Qur'an puts it in 39:10, and as translated by Muhammad Asad, is "beyond all reckoning".  The test of life is specifically for adults in full possession of their mental faculties. Children may suffer, and are observed to suffer, given the nature of life but they are believed to be completely free from sin and liability. Divine justice is affirmed through the theory of compensation. All sufferers will be compensated. This includes non-believers and, more importantly, children, who are destined to go to Paradise.  The doctrine of 'Adl in the words of ʿAbd al-Jabbar: It is the knowledge that God is removed from all that is morally wrong ("qabih") and that all his acts are morally good ("hasana"). This is explained by the fact that you know that all human acts of injustice ("zulm"), transgression ("jawr"), and the like cannot be of his creation ("min khalqihi"). Whoever attributes that to him has ascribed to him injustice and insolence ("safah") and thus strays from the doctrine of justice. And you know that God does not impose faith upon the unbeliever without giving him the power ("al-qudra") for it, nor does he impose upon a human what he is unable to do, but he only gives to the unbeliever to choose unbelief on his own part, not on the part of God. And you know that God does not will, desire or want disobedience. Rather, he loathes and despises it and only wills obedience, which he wants and chooses and loves. And you know that he does not punish the children of polytheists ("al-mushrikin") in Hellfire because of their fathers' sin, for he has said: "Each soul earns but its own due" (Qur'an 6:164); and he does not punish anyone for someone else's sin because that would be morally wrong ("qabih"), and God is far removed from such. And you know that he does not transgress his rule (hukm) and that he only causes sickness and illness in order to turn them to advantage. Whoever says otherwise has allowed that God is iniquitous and has imputed insolence to him. And you know that, for their sakes, he does the best for all of his creatures, upon whom he imposes moral and religious obligations ("yukallifuhum"), and that He has indicated to them what he has imposed upon them and clarified the path of truth so that we could pursue it, and he has clarified the path of falsehood ("tariq l-batil") so that we could avoid it. So, whoever perishes does so only after all this has been made clear. And you know that every benefit we have is from God; as he has said: "And you have no good thing that is not from Allah" (Qur'an 16:53); it either comes to us from him or from elsewhere. Thus, when you know all of this you become knowledgeable about justice from God.

Promise and warning.

This comprised questions of the Last day, or in Arabic, the Qiyamah (Day of Judgment). According to 'Abd al-Jabbar, The doctrine of irreversible Divine promises and warnings, is fashioned out the Islamic philosophy of human existence. Humans, (or "insan" in Arabic) are created with an innate need in their essence to submit themselves to something. Also, it is seen as an innate need of all humans to pursue an inner peace and contentment within the struggles of an imperfect world. Knowledge of God, truth, and choices, in relation to one's innate need of submission is seen in Islam as the promise and recompense of God ("al-thawab") to those who follow. His warning is looked at as a conscious decision by a human submitting themselves, and choosing a varying principle which he had given a clear warning to. He will not go back on his word, nor can he act contrary to his promise and warning, nor lie in what he reports, in contrast to what the Postponers (Murjites) hold.

Intermediate position.

That is, Muslims who commit grave sins and die without repentance are not considered as mu'mins (believers), nor are they considered kafirs (non-believers), but in an intermediate position between the two. The reason behind this is that a mu'min is, by definition, a person who has faith and conviction in and about God, and who has his/her faith reflected in his/her deeds and moral choices. Any shortcoming on any of these two fronts makes one, by definition, not a mu'min. On the other hand, one does not become a "kafir" (i.e. rejecter; non-believer), for this entails, inter alia, denying the Creator — something not necessarily done by a committer of a grave sin. The fate of those who commit grave sins and die without repentance is Hell. Hell is not considered a monolithic state of affairs but as encompassing many degrees to accommodate the wide spectrum of human works and choices, and the lack of comprehension associated to The Ultimate Judge (one of the other names in Islam of God.) Consequently, those in the intermediate position, though in Hell, would have a lesser punishment because of their belief and other good deeds. Muʿtazilites adopted this position as a middle ground between Kharijites and Murjites. In the words of ʿAbd al-Jabbar, the doctrine of the intermediate position is the knowledge that whoever murders, or fornicates ("zina"), or commits serious sins is a grave sinner ("fasiq") and not a believer, nor is his case the same that of believers with respect to praise and attributing greatness, since he is to be cursed and disregarded. Nonetheless, he is not an unbeliever who cannot be buried in our Muslim cemetery, or be prayed for, or marry a Muslim. Rather, he has an intermediate position, in contrast to the Seceders (Kharijites) who say that he is an unbeliever, or the Murjites who say that he is a believer.

The enjoining of right and prohibiting of wrong.

These two tenets, like the "intermediate position" follow logically (according to scholar Majid Fakhry) from the basic Muʿtazilite concepts of divine unity, justice and free will, of which they are the logical conclusion. Even though they are accepted by most Muslims, Muʿtazilites give them a specific interpretation in the sense that, even though God enjoins what is right and prohibits what is wrong, the use of reason allows a Muslim in most cases to identify for himself what is right and what is wrong, even without the help of revelation. Only for some acts is the revelation necessary to determine whether a certain act is right or wrong. This is discussed in further details below.

The use of reasoning and logic.

Muʿtazilites based the analysis of all religious texts and doctrines to be analysed by sane mind and solid logic and if there is a discrepancy then the texts or doctrines should be rejected. This part alone made them the enemy of state and orthodox Muslims who conservatively follow the Hadith (by far the majority of Muslims today, including all Sunni and Shia sects).

Theory of interpretation.

Muʿtazilah relied on a synthesis between reason and revelation. That is, their rationalism operated in the service of scripture and Islamic theological framework. They, as the majority of Muslim jurist-theologians, validated allegorical readings of scripture whenever necessary. Justice ʿAbd al-Jabbar (935-1025) said in his "Sharh al-Usul al-Khamsa" (The Explication of the Five Principles):  The hermeneutic methodology proceeds as follows: if the literal meaning of an ayah (verse) is consistent with the rest of scripture, the main themes of the Qur'an, the basic tenets of the Islamic creed, and the well-known facts, then interpretation, in the sense of moving away from the literal meaning, is not justified. If a contradiction results from adopting the literal meaning, such as a literal understanding of the "hand" of God that contravenes his transcendence and the Qur'anic mention of his categorical difference from all other things, then an interpretation is warranted. In the above quote, Justice 'Abd al-Jabbar emphatically mentioned that if there are two possible interpretations, both capable of resolving the apparent contradiction created by literal understanding of a verse, then the interpretation closer to the literal meaning should take precedence, for the relationship between the interpretations, close and distant, becomes the same as the literal understanding and the interpretation.  Note: Sharh al-Usul al-Khamsah may be a paraphrase or supercommentary made by Abd al-Jabbar's student Mankdim.

The first obligation.

Muʿtazilis believed that the first obligation on humans, specifically adults in full possession of their mental faculties, is to use their intellectual power to ascertain the existence of God, and to become knowledgeable of his attributes. One must wonder about the whole existence, that is, about why something exists rather than nothing. If one comes to know that there is a being who caused this universe to exist, not reliant on anything else and absolutely free from any type of need, then one realizes that this being is all-wise and morally perfect. If this being is all-wise, then his very act of creation cannot be haphazard or in vain. One must then be motivated to ascertain what this being wants from humans, for one may harm oneself by simply ignoring the whole mystery of existence and, consequently, the plan of the Creator. This paradigm is known in Islamic theology as "wujub al-nazar", i.e., the obligation to use one's speculative reasoning to attain ontological truths. About the "first duty," ʿAbd al-Jabbar said it is "speculative reasoning ("al-nazar") which leads to knowledge of God, because he is not known by the way of necessity ("daruratan") nor by the senses ("bi l-mushahada"). Thus, he must be known by reflection and speculation."  The difference between Muʿtazilis and other Muslim theologians is that Muʿtazilis consider "al-nazar" an obligation even if one does not encounter a fellow human being claiming to be a messenger from the Creator, and even if one does not have access to any alleged God-inspired or God-revealed scripture. On the other hand, the obligation of "nazar" to other Muslim theologians materializes upon encountering prophets or scripture.

Reason and revelation.

The Muʿtazilis had a nuanced theory regarding reason, Divine revelation, and the relationship between them. They celebrated power of reason and human intellectual power. To them, it is the human intellect that guides a human to know God, his attributes, and the very basics of morality. Once this foundational knowledge is attained and one ascertains the truth of Islam and the Divine origins of the Qur'an, the intellect then interacts with scripture such that both reason and revelation come together to be the main source of guidance and knowledge for Muslims. Harun Nasution in the Muʿtazila and Rational Philosophy, translated in Martin (1997), commented on Muʿtazili extensive use of rationality in the development of their religious views saying: "It is not surprising that opponents of the Muʿtazila often charge the Muʿtazila with the view that humanity does not need revelation, that everything can be known through reason, that there is a conflict between reason and revelation, that they cling to reason and put revelation aside, and even that the Muʿtazila do not believe in revelation. But is it true that the Muʿtazila are of the opinion that everything can be known through reason and therefore that revelation is unnecessary? The writings of the Muʿtazila give exactly the opposite portrait. In their opinion, human reason is not sufficiently powerful to know everything and for this reason humans need revelation in order to reach conclusions concerning what is good and what is bad for them."  The Muʿtazili position on the roles of reason and revelation is well captured by what Abu al-Hasan al-Ash'ari (d. 324 AH/935 AD), the eponym of the Ashʿari school of theology, attributed to the Mu'tazili scholar Ibrahim an-Nazzam (d. 231 AH/845 AD) (1969): In the above formulation, a problem emerged, which is rendering something obligatory on the Divine being — something that seems to directly conflict with Divine omnipotence. The Muʿtazili argument is predicated on absolute Divine power and self-sufficiency, however. Replying to a hypothetical question as to why God does not do that which is ethically wrong ("la yaf`alu al-qabih"), 'Abd al-Jabbar replied: Because he knows the immorality of all unethical acts and that he is self-sufficient without them...For one of us who knows the immorality of injustice and lying, if he knows that he is self-sufficient without them and has no need of them, it would be impossible for him to choose them, insofar as he knows of their immorality and his sufficiency without them. Therefore, if God is sufficient without need of any unethical thing it necessarily follows that he would not choose the unethical based on his knowledge of its immorality. Thus every immoral thing that happens in the world must be a human act, for God transcends doing immoral acts. Indeed, God has distanced himself from that with his saying: "But Allah wills no injustice to his servants" (Qur'an 40:31), and his saying: "Verily Allah will not deal unjustly with humankind in anything" (Qur'an 10:44).  The thrust of ʿAbd al-Jabbar's argument is that acting immorally or unwisely stems from need and deficiency. One acts in a repugnant way when one does not know the ugliness of one's deeds, i.e., because of lack of knowledge, or when one knows but one has some need, material, psychological, or otherwise. Since God is absolutely self-sufficient (a result from the cosmological "proof" of his existence), all-knowing, and all-powerful, he is categorically free from any type of need and, consequently, he never does anything that is ridiculous, unwise, ugly, or evil.  The conflict between Muʿtazilis and Ashʿaris concerning this point was a matter of focus. Muʿtazilis focused on divine justice, whereas the Ashʿaris focused on divine omnipotence. Nevertheless, Divine self-restraint in Muʿtazili discourse is part of divine omnipotence, not a negation of it.

Validity of hadith.

"Ahl al-Kalam" argued that the prophetic example of Muhammad in his capacity as a messenger "is found in following the Quran alone", rather than oral Hadith.  The early Mu'tazilis viewed the transmission of the oral Hadith as not sufficiently reliable. The Hadith, according to them, was mere guesswork, conjecture, and bidah (innovation), while the Quran was complete and perfect, and did not require the Hadith or any other book to supplement or complement it. For example, during the Abassid dynasty, the poet, theologian, and jurist, Ibrahim an-Nazzam founded a madhhab called the Nazzamiyya that rejected the authority of Hadiths. His famous student, Al-Jahiz, was also critical of those who followed oral Hadiths, referring to his Hadithist opponents as "al-nabita" ("the contemptible").  According to Racha El Omari, early Mutazilites believed that hadith were susceptible to "abuse as a polemical ideological tool"; that the "matn" (content) of the hadith -- not just the "isnad" -- ought to be scrutinized for doctrine and clarity; that for hadith to be valid they ought to be "mutawatir", i.e. supported by "tawātur" or many "isnād" (chains of oral transmitters), each beginning with a different Companion.  In writing about "mutawatir" (multi-isnād Hadith) and "ahad" (single-isnad hadith, i.e. almost all hadith) and their importance from the legal theoretician's point of view, Wael Hallaq notes the medieval scholar Al-Nawawi (1233–1277) argued that any non-"mutawatir" hadith is only probable and can not reach the level of certainty that a "mutawatir" hadith can. However, these mutawir were extremely scarce. Scholars like Ibn al-Salah (d. 1245 CE), al-Ansari (d. 1707 CE), and Ibn ‘Abd al-Shakur (d. 1810 CE) found "no more than eight or nine" hadiths that fell into the "mutawatir" category.  Wāṣil ibn ʿAṭāʾ (700–748 CE, by many accounts a founder of the Mutazilite school of thought), held that there was evidence for the veracity of a report when it had four independent transmitters. His assumption was that there could be no agreement between all transmitters in fabricating a report. Wāṣil’s acceptance of tawātur seems to have been inspired by the juridical notion of witnesses as proof that an event did indeed take place. Hence, the existence of a certain number of witnesses precluded the possibility that they were able to agree on a lie, as opposed to the single report which was witnessed by one person only, its very name meaning the “report of one individual” (khabar al-wāḥid). Abū l-Hudhayl al-ʿAllāf (d. 227/841) continued this verification of reports through tawātur, but proposed that the number of witnesses required for veracity be twenty, with the additional requirement that at least one of the transmitters be a believer.  One Mu'tazilite who expressed the strongest statement of skepticism of any source of knowledge outside of reason and the Qurʾān was Ibrahim an-Nazzam (c. 775 – c. 845). For him, both the single and the mutawātir reports could not be trusted to yield knowledge. He recounted contradictory ḥadīth and examined their divergent content (matn) to show why they should be rejected: they relied on both faulty human memory and bias, neither of which could be trusted to transmit what is true. Al-Naẓẓām bolstered his strong refutation of the trustworthiness of ḥadīth within the larger claim that ḥadīth circulated and thrived to support polemical causes of various theological sects and jurists, and that no single transmitter could by himself be held above suspicion of altering the content of a single report. Al-Naẓẓām’s skepticism involved far more than excluding the possible verification of a report, be it single or mutawātir. His stance also excluded the trustworthiness of consensus, which proved pivotal to classical Muʿtazilite criteria devised for verifying the single report (see below). Indeed, his shunning of both consensus and tawātur earned him a special mention for the depth and extent of his skepticism, even among fellow Muʿtazilites.

Muʿtazila ( "") is a rationalist school of Islamic theology that flourished in the cities of Basra and Baghdad, both now in Iraq, during the 8th to the 10th centuries.

Die Muʿtazila () war eine hauptsächlich in Basra und Bagdad vertretene theologische Strömung des Islam, die ihre Blütezeit zwischen dem 9. und 11. Jahrhundert erlebte, stark von der griechischen Philosophie beeinflusst war und sich besonders im Kalām, einer Form des religiösen Streitgesprächs mit rationalen Argumenten, hervortat. Sie stellte die Willensfreiheit des Menschen in den Vordergrund ihrer Lehre. Innerhalb der Muʿtazila gab es verschiedene Lehrrichtungen, die jeweils nach ihrem Haupttheologen benannt waren.