Because they activate the<unk> CB1 and CB2 receptors, many of the effects of<unk>  are similar to those of THC. These are achieved at lower doses, because many<unk>  are more potent than marijuana, and users are often unaware of exactly what they are getting and how potent it is. For example, Δ9-THC has an EC50 of 250 nM at CB1 and 1157 nM at CB2, whereas PB-22 has an EC50 of 5.1 nM at CB1 and 37 nM at CB2. Adverse effects observed due to<unk> use include acute kidney injury, cardiac toxicity, seizure, stroke, tremor, hypokalemia, and rhabdomyolysis. Some negative effects of 5F-PB-22 reported by users included nausea, vomiting, confusion, poor coordination, anxiety, and seizures. Some of the negative effects of 5F-AKB-48 reported by users included palpitations, paranoia, intense anxiety, and a taste like burned plastic. In addition, while there are no fatal overdose cases linked to marijuana, there are deaths linked to<unk>  each year. The most common mechanisms leading to death following<unk> use include behavioral risks, such as self-harm and suicide, falling from a height, and wandering into traffic; cardiovascular effects; and central nervous system depression. Researchers have pointed out a few ways that<unk>  differ from marijuana, and therefore may be more dangerous. First, they often have greater intrinsic activity. Many of the<unk>  are full agonists of the<unk>  receptors, CB1 and CB2, compared to THC, which is only a partial agonist. Secondly, they may have other actions in the body, in addition to activating<unk> receptors. Some may work on NMDA glutamate receptors. Some may also work on serotonin, either indirectly by inhibiting MAO and increasing 5-HT1A receptor expression, or by directly binding to serotonin receptors, including the 5-HT1A and 5-HT3 subtypes; some researchers speculate that this activity may be because the indole moiety that some<unk>  possess is similar to the structure of serotonin. Third,<unk>  may break down into metabolites, or create other by-products when heated, that may differ from marijuana. Phase 1 metabolism of JWH-018 results in at least nine monohydroxylated metabolites, three of which have been shown to be full agonists of the CB1 receptors, compared to the metabolism of THC, which only results in one psychoactive monohydroxylated metabolite. The metabolite N-(3-hydroxypentyl) JWH-018 was found to have toxic effects that its parent compound does not. Some metabolites even appear to be<unk> antagonists. Lastly, they may contain unwanted substances, be mislabeled, or contain different doses than advertised (in one analysis, a difference of one log unit was found). No official studies have been conducted on the effects of<unk>  on humans (as is often the case with illegal and potentially toxic compounds); however, user reports and the effects experienced by patients seeking medical care after taking<unk>  have been published. Each of the many different<unk>  can have different effects at different dosages. The CDC described<unk> overdoses between 2010 and 2015 and of 277 drug overdose patients who reported<unk> as the sole agent, 66.1% reported problems in the central nervous system (e.g., agitation, coma, toxic psychosis), 17% reported cardiovascular problems (e.g., tachycardia, bradycardia), 7.6% reported pulmonary problems (5.4% of which had respiratory depression), and 4% reported acute kidney injury. Four postmortem cases linked to the<unk>  5F-PB-22 have been reviewed. The postmortem blood specimens contained a range of 1.1-1.5 ng/mL of 5F-PB-22. Three of the four cases were sudden episodes and the symptoms leading to death included acute shortness of breath; vasocongestion in the liver, spleen, and kidneys; bilateral pulmonary edema; dead inflamed tissue (necrotizing granulomatous inflammation); and congestion of most internal organs. The fourth case presented to the hospital with severe problems that deteriorated over the course of a day, ending with circulatory, respiratory, central nervous system, and renal failure. Addiction There have been reports of a strong compulsion to re-dose, withdrawal symptoms, and persistent cravings lasting up to a week after taking<unk> , indicating that<unk>  may be more addictive than marijuana. Psychosis Studies are currently available that suggest an association between<unk>  and psychosis. The use of<unk>  can be associated with psychosis and physicians are beginning to investigate if some patients with inexplicable psychotic symptoms may have at one point used<unk> . In contrast to most other recreational drugs, the dramatic psychotic state induced by use of<unk>  has been reported, in multiple cases, to persist for several weeks, and in one case for seven months, after complete cessation of drug use. Some studies suggest that not only can<unk>  induce psychosis, but they can worsen previously stable psychotic disorders and might trigger a chronic (long-term) psychotic disorder among vulnerable individuals such as those with a family history of mental illness. Individuals with risk factors for psychotic disorders are often counseled against using<unk> . Psychiatrists have suggested that the lack of an antipsychotic chemical, like CBD in natural cannabis, may make<unk>  more likely to induce psychosis than natural cannabis.
Synthetic cannabinoids
Substituted amphetamine
Psychedelic drug
Amphetamine type stimulant
Heroic medicine
Querulant
Byzantine medicine
Substituted tryptamine