Psychomotor performance in relation to acute oral administration of Δ9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Neural Basis of Δ-9-Tetrahydrocannabinol and Cannabidiol: Effects During Response Inhibition Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Cannabinoids in the management of difficult to treat pain Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis Controlled clinical trial of cannabidiol in Huntington's disease The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. A double-blind trial of delta 9-tetrahydrocannabinol in primary anorexia nervosa. Treatment of Tourette Syndrome with Delta-9-Tetrahydrocannabinol (Δ9-THC): No Influence on Neuropsychological Performance Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia
Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users . The high levels of central cannabinoid ( CB1 ) receptors in the basal ganglia , the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity . Based on the close relationship between cannabis use , the endogenous cannabinoid system and motor disturbances found in schizophrenia , we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients . This prospect i ve , double-blind , placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-h and ed volunteers ( age 27.9 ± 2.9 years , 12 male ) by comparing Δ9-tetrahydrocannabinol ( Δ9-THC ) and st and ardized cannabis extract containing Δ9-THC and cannabidiol .  Psychomotor performance was assessed by using a finger tapping test series . Cannabis extract , but not Δ9-THC , revealed a significant reduction of right-h and tapping frequencies that was also found in schizophrenia . As to the pure Δ9-THC condition , left-h and tapping frequencies were correlated with the plasma concentrations of the Δ9-THC metabolite 11-OH-THC . These effects are thought to be related to cannabinoid actions on CB1 receptors in the basal ganglia , the cerebral cortex and the cerebellum . Our data further demonstrate that acute CB1 receptor activation under the cannabis extract condition may also affect intermanual coordination ( IMC ) as an index of interhemispheric transfer . AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve . This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum INTRODUCTION Cannabis and agonists of the brain cannabinoid receptor ( CB1R ) produce acute  memory impairments in humans . However , the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans . The objective of this analysis was to determine whether the administration of Δ9-Tetrahydrocannabinol ( THC ) , the principal psychoactive constituent of cannabis , impairs encoding and /or retrieval of verbal information . MATERIAL S AND METHODS Healthy subjects were recruited from the community . Subjects were administered the Rey-Auditory Verbal Learning Test ( RAVLT ) either before administration of THC ( experiment # 1 ) ( n=38 ) or while under the influence of THC ( experiment # 2 ) ( n=57 ) . Immediate and delayed recall on the RAVLT was compared . Subjects received intravenous THC , in a placebo-controlled , double-blind , r and omized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication . RESULTS Total immediate recall , short delayed recall , and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC ( experiment # 2 ) and not when the RAVLT was administered prior . CONCLUSIONS THC acutely interferes with encoding of verbal memory without interfering with retrieval . These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information . Future studies will be necessary to determine whether THC impairs encoding of non-verbal information , to what extent THC impairs memory consolidation , and the role of other cannabinoids in the memory-impairing effects of cannabis . CLINICAL TRIAL INFORMATION Cannabinoids , Neural Synchrony , and Information Processing ( THC-Gamma ) http:// clinical trials.gov/ct2/show/ study /NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http:// clinical trials.gov/ct2/show/NCT00678730 NCT00678730 Recent advances in the underst and ing of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis . In a 3-day , double-blind , r and omized , and counterbalanced study , the behavioral , cognitive , and endocrine effects of 0 , 2.5 , and 5 mg intravenous delta-9-tetrahydrocannabinol ( Δ-9-THC ) were characterized in 22 healthy individuals , who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder . Prospect i ve safety data at 1 , 3 , and 6 months post study was also collected . Δ-9-THC ( 1 ) produced schizophrenia-like positive and negative symptoms ; ( 2 ) altered perception ; ( 3 ) increased anxiety ; ( 4 ) produced euphoria ; ( 5 ) disrupted immediate and delayed word recall , sparing recognition recall ; ( 6 ) impaired performance on tests of distractibility , verbal fluency , and working memory ( 7 ) did not impair orientation ; ( 8) increased plasma cortisol . These data indicate that Δ-9-THC produces a broad range of transient symptoms , behaviors , and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses . These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders Objectives : To determine whether plant-derived cannabis medicinal extracts ( CME ) can alleviate neurogenic symptoms unresponsive to st and ard treatment , and to quantify adverse effects . Design : A consecutive series of double-blind , r and omized , placebo-controlled single-patient cross-over trials with two-week treatment periods . Setting : Patients attended as out patients , but took the CME at home . Subjects : Twenty-four patients with multiple sclerosis ( 18 ) , spinal cord injury ( 4 ) , brachial plexus damage ( 1 ) , and limb amputation due to neurofibromatosis ( 1 ) . Intervention : Whole-plant extracts of delta-9-tetrahydrocannabinol ( THC ) , cannabidiol ( CBD ) , 1:1 CBD : THC , or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5–120 mg/24 hours . Measures used : Patients recorded symptom , well-being and intoxication scores on a daily basis using visual analogue scales . At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales , administered st and ard measures of disability ( Barthel Index ) , mood and cognition , and recorded adverse events . Results : Pain relief associated with both THC and CBD was significantly superior to placebo . Impaired bladder control , muscle spasms and spasticity were improved by CME in some patients with these symptoms . Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME . Conclusions : Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to st and ard treatments . Unwanted effects are predictable and generally well tolerated . Larger scale studies are warranted to confirm these findings BACKGROUND Central neuropathic pain ( CNP ) , pain initiated or caused by a primary lesion or dysfunction of the central nervous system , occurs in ~28 % of patients with multiple sclerosis ( MS ) . Delta(9)-Tetrahydrocannabinol/cannabidiol ( THC/CBD ) , an endocannabinoid system modulator , has demonstrated efficacy for up to 4 weeks in r and omized controlled trials in the treatment of CNP in patients with MS . OBJECTIVE The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD ( Sativex ( R ) , GW Pharmaceuticals plc , Salisbury , United Kingdom ) oromucosal spray in CNP associated with MS . METHODS This uncontrolled , open-label trial was an indefinite- duration extension of a previously reported 5-week r and omized study in patients with MS and CNP . In the initial trial , patients were r and omized to placebo or THC/CBD . Patients were only required to maintain their existing analgesia in the r and omized study . In the open-label trial they could vary their other analgesia as required . All patients ( placebo and THC/CBD ) who completed the r and omized trial commenced the open-label follow-up on THC/CBD ( 27 mg/mL : 25 mg/mL ) . Patients titrated their dosage , maintaining their existing analgesia . The primary end point of the trial was the number , frequency , and type of adverse events ( AEs ) reported by patients . Secondary end points included changes from baseline in 11-point numerical rating scale ( NRS-11 ) neuropathic pain score , hematology and clinical chemistry test results , vital signs , trial drug usage , and intoxication visual analogue scale scores . RESULTS Sixty-six patients were enrolled in the r and omized trial ; 64 ( 97 % ) completed the r and omized trial and 63 ( 95 % ) entered the open-label extension ( race , white , 100 % ; sex , male , 14 [ 22 % ] ; mean [ SD ] age , 49 [ 8.4 ] years [ range , 27 - 71 years [ ) . The mean ( SD ) duration of open-label treatment was 463 ( 378 ) days ( median , 638 days ; range , 3 - 917 days ) , with 34 ( 54 % ) patients completing > 1 year of treatment with THC/CBD and 28 ( 44 % ) patients completing the open-label trial with a mean ( SD ) duration of treatment of 839 ( 42 ) days ( median , 845 days ; range , 701 - 917 days ) . Mean NRS-11 pain scores in the final week of the r and omized trial were 3.8 in the treatment group and 5.0 in the placebo group . In the 28 ( 44 % ) patients who completed the 2-year follow up , the mean ( SD ) NRS-11 pain score in the final week of treatment was 2.9 ( 2.0 ) ( range , 0 - 8.0 ) . Fifty-eight ( 92 % ) patients experienced > or = 1 treatment-related AE . These AEs were rated by the investigator as mild in 47 ( 75 % ) patients , moderate in 49 ( 78 % ) , and severe in 32 ( 51 % ) . The most commonly reported AEs were dizziness ( 27 % ) , nausea ( 18 % ) , and feeling intoxicated ( 11 % ) . Two treatment-related serious AEs ( ventricular bigeminy and circulatory collapse ) were judged to be treatment-related . Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation . Eleven ( 17 % ) patients experienced oral discomfort , 4 persistently . Regular oral examinations revealed that 7 ( 11 % ) patients developed white buccal mucosal patches and 2 ( 3 % ) developed red buccal mucosal patches ; all cases were deemed mild and resolved . Seventeen ( 25 % ) patients withdrew due to AEs . The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial . CONCLUSIONS THC/CBD was effective , with no evidence of tolerance , in these select patients with CNP and MS who completed approximately 2 years of treatment ( n = 28 ) . Ninety-two percent of patients experienced an AE , the most common of which were dizziness and nausea . The majority of AEs were deemed to be of mild to moderate severity by the investigators BACKGROUND This study examined the effect of Delta-9-tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) on brain activation during a motor inhibition task . METHODS Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind , pseudo-r and omized , placebo-controlled repeated measures within-subject design . RESULTS Relative to placebo , THC  attenuated activation in the right inferior frontal and the anterior cingulate gyrus . In contrast , CBD  deactivated the left temporal cortex and insula . These effects were not related to changes in anxiety , intoxication , sedation , and psychotic symptoms . CONCLUSIONS These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition . CBD modulated function in regions not usually implicated in response inhibition CONTEXT Cannabis use can both increase and reduce anxiety in humans . The neurophysiological substrates of these effects are unknown . OBJECTIVE To investigate the effects of 2 main psychoactive constituents of Cannabis sativa ( Delta9-tetrahydrocannabinol [ Delta9-THC ] and cannabidiol [ CBD ] ) on regional brain function during emotional processing . DESIGN Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety . Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC , 600 mg of CBD , or a placebo in a double-blind , r and omized , placebo-controlled design . PARTICIPANTS Fifteen healthy , English-native , right-h and ed men who had used cannabis 15 times or less in their life . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygenation level-dependent response ) , electrodermal activity ( skin conductance response [ SCR ] ) , and objective and subjective ratings of anxiety . RESULTS Delta9-Tetrahydrocannabinol increased anxiety , as well as levels of intoxication , sedation , and psychotic symptoms , whereas there was a trend for a reduction in anxiety following administration of CBD . The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD . Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces , and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations . Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas . CONCLUSIONS Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural , electrodermal , and symptomatic response to fearful faces . The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety , whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions This article review s recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms , as well as r and omized clinical trials employing cannabinoids in pain treatment .  Tetrahydrocannabinol ( THC , Marinol ® ) and nabilone ( Cesamet ® ) are currently approved in the United States and other countries , but not for pain indications . Other synthetic cannabinoids , such as ajulemic acid , are in development . Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation . Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC ( partial CB1 receptor agonist ) and cannabidiol ( CBD , a non-euphoriant , anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects ) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis , and in 2007 for intractable cancer pain . Numerous r and omized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain , rheumatoid arthritis and cancer pain . An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006 . Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles . Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise Objective : To test the effectiveness and long term safety of cannabinoids in multiple sclerosis ( MS ) , in a follow up to the main Cannabinoids in Multiple Sclerosis ( CAMS ) study . Methods : In total , 630 patients with stable MS with muscle spasticity from 33 UK centres were r and omised to receive oral Δ9-tetrahydrocannabinol ( Δ9-THC ) , cannabis extract , or placebo in the main 15 week CAMS study . The primary outcome was change in the Ashworth spasticity scale . Secondary outcomes were the Rivermead Mobility Index , timed 10 metre walk , UK Neurological Disability Score , postal Barthel Index , General Health Question naire-30 , and a series of nine category rating scales . Following the main study , patients were invited to continue medication , double blinded , for up to12 months in the follow up study reported here . Results : Intention to treat analysis of data from the 80 % of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months ( Δ9-THC mean reduction 1·82 ( n = 154 , 95 % confidence interval ( CI ) 0.53 to 3.12 ) , cannabis extract 0.10 ( n = 172 , 95 % CI −0.99 to 1.19 ) , placebo −0.23 ( n = 176 , 95 % CI −1.41 to 0.94 ) ; p = 0.04 unadjusted for ambulatory status and centre , p = 0.01 adjusted ) . There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability . There were no major safety concerns . Overall , patients felt that these drugs were helpful in treating their disease . Conclusions : These data provide limited evidence for a longer term treatment effect of cannabinoids . A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS Abstract Central neuropathic pain ( CNP ) occurs in many multiple sclerosis ( MS ) patients . The provision of adequate pain relief to these patients can very difficult . Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol ( CBD ) oromucosal spray ( USAN name , nabiximols ; Sativex , GW Pharmaceuticals , Salisbury , Wiltshire , UK ) , to alleviate CNP . Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment , in a double-blind manner , for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain . This parallel-group phase of the study was then followed by an 18-week r and omized-withdrawal study ( 14-week open-label treatment period plus a double-blind 4-week r and omized-withdrawal phase ) to investigate time to treatment failure and show maintenance of efficacy . A total of 339 patients were r and omized to phase A ( 167 received THC/CBD spray and 172 received placebo )  . Of those who completed phase A , 58 entered the r and omized-withdrawal phase . The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met , with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo ( p = 0.234 ) . However , an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point ( p = 0.046 ) . During the r and omized-withdrawal phase , the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray , with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group ( p = 0.04 ) . The mean change from baseline in Pain Numerical Rating Scale ( NRS ) ( p = 0.028 ) and sleep quality NRS ( p = 0.015 ) scores , both secondary endpoints in phase B , were also statistically significant compared to placebo , with estimated treatment differences of −0.79 and 0.99 points , respectively , in favor of THC/CBD spray treatment . The results of the current investigation were equivocal , with conflicting findings in the two phases of the study . While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period , the primary endpoint was not met due to a similarly large number of placebo responders . In contrast , there was a marked effect in phase B of the study , with an increased time to treatment failure in the THC/CBD spray group compared to placebo . These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients Based on encouraging preliminary findings , cannabidiol ( CBD ) , a major nonpsychotropic constituent of Cannabis , was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington 's Disease ( HD ) . The effects of oral CBD ( 10 mg/kg/day for 6 weeks ) and placebo ( sesame oil for 6 weeks ) were ascertained weekly under a double-blind , r and omized cross-over design . A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables , and on a Cannabis side effect inventory , clinical lab tests and other safety outcome variables , indicated no significant ( p greater than 0.05 ) or clinical ly important differences . Correspondingly , plasma levels of CBD  were assayed by GC/MS , and the weekly levels ( mean range of 5.9 to 11.2 ng/ml ) did not differ significantly over the 6 weeks of CBD administration . In summary , CBD , at an average daily dose of about 700 mg/day for 6 weeks , was neither symptomatically effective nor toxic , relative to placebo , in neuroleptic-free patients with HD BACKGROUND Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia , dissociative states , and other psychiatric conditions . Cannabidiol ( CBD ) , a cannabinoid-1/2 ( CB1/2 ) receptor weak partial agonist or antagonist , may play a role in the treatment of schizophrenia . OBJECTIVE This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist , ketamine , in healthy human subjects . METHODS Ten male healthy volunteers were evaluated twice in a r and omized order . In both sessions they received ketamine ( bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25mg/kg over 30 min ) preceded by either CBD ( 600 mg ) or placebo . Psychopathology was assessed using the Brief Psychiatric Rating Scale ( BPRS ) and the CADSS ( Clinician Administered Dissociative States Scale ) at regular intervals from 30 min before to 90 min after ketamine administration . RESULTS CBD significantly augmented the activating effects of ketamine , as measured by the activation subscales of the BPRS . However , CBD also showed a non-significant trend to reduce ketamine-induced depersonalization , as measured by the CADSS . CONCLUSION These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol .  Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively Δ9-Tetrahydrocannabinol ( Δ9-THC ) , the most prominent psychoactive cannabinoid in Cannabis sativa L. ( marijuana ) , has been reported to have properties of appetite stimulation , promotion of weight gain , and antiemetic efficacy in selected patient population s. In this 4-week , double-blind , crossover study , 11 female patients with primary anorexia nervosa ( PAN ) were evaluated on Δ9-THC and on an active placebo , diazepam . All patients participated in a st and ardized behavior modification treatment program . The following data were obtained : ( 1 ) daily weight , ( 2 ) daily caloric intake , and ( 3 ) weekly psychiatric assessment s. The two groups were comparable on all measures at baseline except for two items on the behavioral rating scales . The only significant differences found between the changes over time on Δ9-THC versus diazepam were more pathology on Δ9-THC for somatization , interpersonal sensitivity , and sleep disturbance . Three patients experienced severe dysphoric reactions consisting of paranoid ideation and feelings of loss of control during Δ9-THC administration . One week after the study ended , each subject was given the highest dose level of Δ8-THC achieved in the study , and periodic blood sample s were obtained coincident with self-rated “ subjective high ” assessment s and pulse measurements . Quantitative analyses of these sample s indicated peak times of 1 to 5 hours postdose for Δ9- THC and for its primary active metabolite , 11-hydroxy-THC , which generally coincided with peak times for “ subjective high ” and pulse rate . The results of this clinical investigation suggest that Δ9-THC is not efficacious , in short-term administration , in the treatment of primary anorexia nervosa and is associated with significant psychic disturbance in some PAN patients Previous studies provide evidence that marijuana ( Cannabis sativa ) and delta-9-tetrahydrocannabinol ( Δ9-THC ) , the major psychoactive ingredient of marijuana , respectively , are effective in the treatment of tics and behavioral problems in Tourette syndrome ( TS ) . It , therefore , has been speculated that the central cannabinoid receptor system might be involved in TS pathology . However , in healthy marijuana users there is an ongoing debate as to whether the use of cannabis causes acute and /or long-term cognitive deficits . In this r and omized double-blind placebo-controlled study , we investigated the effect of a treatment with up to 10 mg Δ9-THC over a 6-week period on neuropsychological performance in 24 patients suffering from TS . During medication and immediately as well as 5–6 weeks after withdrawal of Δ9-THC treatment , no detrimental effect was seen on learning curve , interference , recall and recognition of word lists , immediate visual memory span , and divided attention . Measuring immediate verbal memory span , we even found a trend towards a significant improvement during and after treatment . Results from this study corroborate previous data suggesting that in patients suffering from TS , treatment with Δ9-THC  causes neither acute nor long-term cognitive deficits . Larger and longer- duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS BACKGROUND Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders . METHODS In a 3-day , double-blind , r and omized , placebo-controlled study , the behavioral , cognitive , motor , and endocrine effects of 0 mg , 2.5 mg , and 5 mg intravenous Delta-9-tetrahydrocannabinol ( Delta-9-THC ) were characterized in 13 stable , antipsychotic-treated schizophrenia patients . These data were compared with effects in healthy subjects reported elsewhere . RESULTS Delta-9-tetrahydrocannabinol transiently increased 1 ) learning and recall deficits ; 2 ) positive , negative , and general schizophrenia symptoms ; 3 ) perceptual alterations ; 4 ) akathisia , rigidity , and dyskinesia ; 5 ) deficits in vigilance ; and 6 ) plasma prolactin and cortisol .  Schizophrenia patients were more vulnerable to Delta-9-THC effects on recall relative to control subjects . There were no serious short- or long-term adverse events associated with study participation . CONCLUSIONS Delta-9-tetrahydrocannabinol is associated with transient exacerbation in core psychotic and cognitive deficits in schizophrenia . These data do not provide a reason to explain why schizophrenia patients use or misuse cannabis . Furthermore , Delta-9-THC might differentially affect schizophrenia patients relative to control subjects . Finally , the enhanced sensitivity to the cognitive effects of Delta-9-THC warrants further study into whether brain cannabinoid receptor dysfunction contributes to the pathophysiology of the cognitive deficits associated with schizophrenia Rationale Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today . Current treatment options are few and limited due to substantial side effects . Objectives The aim of the study was to measure the effect of the cannabinoid dronabinol on nocturnal motor activity . Methods In an open-label pilot study , six consecutive patients in the late stages of dementia and suffering from circadian and behavioral disturbances — five patients with Alzheimer ’s disease and one patient with vascular dementia — were treated with 2.5 mg dronabinol daily for 2 weeks . Motor activity was measured objective ly using actigraphy . Results Compared to baseline , dronabinol led to a reduction in nocturnal motor activity ( P=0.028 ) . These findings were corroborated by improvements in Neuropsychiatric Inventory total score ( P=0.027 ) as well as in subscores for agitation , aberrant motor , and nighttime behaviors ( P<0.05 ) . No side effects were observed . Conclusions The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients . Thus , it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementia
This review finds no evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia .
BACKGROUND Following the discovery of an endogenous cannabinoid system and the identification of specific cannabinoid receptors in the central nervous system , much work has been done to investigate the main effects of these compounds .
There is increasing evidence that the cannabinoid system may regulate neurodegenerative processes such as excessive glutamate production , oxidative stress and neuroinflammation .
Neurodegeneration is a feature common to the various types of dementia and this has led to interest in whether cannabinoids may be clinical ly useful in the treatment of people with dementia .
Recent studies have also shown that cannabinoids may have more specific effects in interrupting the pathological process in Alzheimer 's disease .
OBJECTIVES To determine from available research whether cannabinoids are clinical ly effective in the treatment of dementia .