Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms A double-blind trial of delta 9-tetrahydrocannabinol in primary anorexia nervosa. Cannabis use and transition to psychosis in people at ultra-high risk. Age‐varying effects of cannabis use frequency and disorder on symptoms of psychosis, depression and anxiety in adolescents and adults Cannabidiol in Humans—The Quest for Therapeutic Targets Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Cannabis use and expression of mania in the general population. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial A multi-center, randomized controlled trial of a group psychological intervention for psychosis with comorbid cannabis dependence over the early course of illness Psychomotor performance in relation to acute oral administration of Δ9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects The impact of cannabis use on clinical outcomes in recent onset psychosis. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Cannabis abuse and the course of recent onset schizophrenic disorders
Objective To determine whether use of cannabis in adolescence increases the risk for psychotic outcomes by affecting the incidence and persistence of sub clinical expression of psychosis in the general population ( that is , expression of psychosis below the level required for a clinical diagnosis ) . Design Analysis of data from a prospect i ve population based cohort study in Germany ( early developmental stages of psychopathology study ) . Setting Population based cohort study in Germany . Participants 1923 individuals from the general population , aged 14 - 24 at baseline . Main outcome measure Incidence and persistence of subthreshold psychotic symptoms after use of cannabis in adolescence .  Cannabis use and psychotic symptoms were assessed at three time points ( baseline , T2 ( 3.5 years ) , T3 ( 8.4 years ) ) over a 10 year follow-up period with the Munich version of the composite international diagnostic interview ( M-CIDI ) . Results In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline , incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 ( adjusted odds ratio 1.9 , 95 % confidence interval 1.1 to 3.1 ; P=0.021 ) . Furthermore , continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 ( 2.2 , 1.2 to 4.2 ; P=0.016 ) . The incidence rate of psychotic symptoms over the period from baseline to T2 was 31 % ( 152 ) in exposed individuals versus 20 % ( 284 ) in non-exposed individuals ; over the period from T2 to T3 these rates were 14 % ( 108 ) and 8 % ( 49 ) , respectively . Conclusion Cannabis use is a risk factor for the development of incident psychotic symptoms . Continued cannabis use might increase the risk for psychotic disorder by impacting on the persistence of symptoms BACKGROUND Cannabis can induce transient psychotic symptoms , but not all users experience these adverse effects . We compared the neural response to Δ9-tetrahydrocannabinol ( THC ) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms . Method In a double-blind , placebo-controlled , pseudor and omized design , 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo , orally . Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task . RESULTS The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic ( TP ; n = 11 ) and non-psychotic ( NP ; n = 10 ) groups . During the THC condition , TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus , the left and right middle temporal gyri and in the right cerebellum . In these regions , THC had opposite effects on activation relative to placebo in the two groups . The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum , independent of the effects of THC . CONCLUSIONS In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC , we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum , suggesting that these regions mediate the effects of the drug on psychotic symptoms Papers pp 1195 , 1199 The strongest evidence that cannabis use may be a risk factor for later psychosis  comes from a Swedish cohort study which found that heavy cannabis use at age 18 increased the risk of later schizophrenia sixfold . 1 2 This study could not establish whether adolescent cannabis use was a consequence of pre-existing psychotic symptoms rather than a cause . We present the first prospect i ve longitudinal study of adolescent cannabis use as a risk factor for  adult schizophreniform disorder  , taking into account childhood psychotic symptoms3 antedating cannabis use . View this table : Association between  cannabis use in adolescence and schizophrenia and depressive symptoms and disorders at age 26 ( n=759 ) , controlling for childhood psychotic symptoms and use of other drugs in adolescence The Dunedin multidisciplinary health and development study ( a study of a general population birth cohort of 1037 individuals born in Dunedin , New Zeal and , in 1972 - 3)4 has a 96 % follow up rate at age 26 . It obtained information on psychotic symptoms at age 11 and drug use at ages 15 and 18 from self reports and assessed The main active ingredient in cannabis , delta-9-tetrahydrocannabinol ( THC ) , can acutely induce psychotic symptoms and impair episodic and working memory . Another major constituent , cannabidiol ( CBD ) , may attenuate these effects . This study aim ed to determine the effects of THC and CBD , both alone and in combination on psychotic symptoms and memory function . A r and omised , double-blind crossover design compared the effects of ( i ) placebo , ( ii ) THC 8 mg , ( iii ) CBD 16 mg and ( iv ) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser . Using an experimental medicine approach to predict treatment sensitivity , we selected 48 cannabis users from the community on the basis of ( 1 ) schizotypal personality question naire scores ( low , high ) and ( 2 ) frequency of cannabis use ( light , heavy ) . The Brief Psychiatric Rating Scale ( BPRS ) , Psychotomimetic States Inventory ( PSI ) , immediate and delayed prose recall ( episodic memory ) , 1- and 2-back ( working memory ) were assessed on each day . Results indicated that THC increased overall scores on the PSI , negative symptoms on BPRS , and robustly impaired episodic and working memory . Co-administration of CBD did not attenuate these effects . CBD alone reduced PSI scores in light users only . At a ratio of 2:1 , CBD does not attenuate the acute psychotic and memory impairing effects of vaporised THC . Frequent cannabis users may show a blunted anti- psychotic response to CBD , which is of concern due to the high rates of cannabis use disorders in patients with schizophrenia 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 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 BACKGROUND Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear . The objective of this study was to assess prospect ively the influence of cannabis use on transition to psychosis in people at ultra-high risk ( UHR ) for the disorder . METHOD Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people ( 104 male , 78 female ) at UHR for psychosis . Individuals were then followed clinical ly for 2 years to determine their clinical outcomes . RESULTS Lifetime cannabis use was reported by 134 individuals ( 73.6 % ) . However , most of these individuals had stopped using cannabis before clinical presentation ( n=98 , 73.1 % ) , usually because of adverse effects . Among lifetime users , frequent use , early-onset use and continued use after presentation were all associated with an increase in transition to psychosis . Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently ( frequent early-onset use : 25 % ; infrequent or late-onset use : 5 % ; χ(2)1=10.971 , p=0.001 ) . However , within the whole sample , cannabis users were no more likely to develop psychosis than those who had never used cannabis ( cannabis use : 12.7 % ; no use : 18.8 % ; χ(2)1=1.061 , p=0.303 ) . CONCLUSIONS In people at UHR for psychosis , lifetime cannabis use was common but not related to outcome . Among cannabis users , frequent use , early-onset use and continued use after clinical presentation were associated with transition to psychosis Abstract Aims We tested the age‐varying associations of  cannabis use ( CU ) frequency and disorder ( CUD ) with  psychotic , depressive and anxiety symptoms in adolescent and adult sample s. Moderating effects of early onset ( ≤ 15 years ) and sex were tested . Design Time‐varying effect models were used to assess the significance of concurrent associations between CU and CUD  and symptoms of psychosis , depression and anxiety at each age . Setting and Participants Adolescent data ( V‐HYS ; n = 662 ) were collected from a r and omly recruited sample of adolescents in Victoria , British Columbia , Canada during a 10‐year period ( 2003–13 ) . Adult cross‐sectional data ( NESARC‐III ; n = 36 309 ) were collected from a representative sample from the United States ( 2012–13 ) .  Measurements Mental health symptoms were assessed using self‐report measures of diagnostic symptoms . CU was based on frequency of past‐year use . Past‐year CUD was based on DSM‐5 criteria . Findings For youth in the V‐HYS , CU was associated with psychotic symptoms following age 22 [ b = 0.13 , 95 % confidence interval ( CI ) = 0.002 , 0.25 ] , with depressive symptoms from ages 16–19 and following age 25 ( b = 0.17 , 95 % CI = 0.003 , 0.34 ) , but not with anxiety symptoms . CUD was associated with psychotic symptoms following age 23 ( b = 0.51 , 95 % CI = 0.01 , 1.01 ) , depressive symptoms at ages 19–20 and following age 25 ( b = 0.71 , 95 % CI = 0.001 , 1.42 ) and anxiety symptoms ages 26–27 only . For adults in the NESARC‐III , CU was associated with mental health symptoms at most ages [ e.g. psychotic symptoms ; age 18 ( b = 0.22 , 95 % CI = 0.10 , 0.33 ) to age 65 ( b = 0.36 , 95 % CI = 0.16 , 0.56 ) ] . CUD was associated with all mental health symptoms across most ages [ e.g. depressive symptoms ; age 18 ( b = 0.96 , 95 % CI = 0.19 , 1.73 ) to age 61 ( b = 1.11 , 95 % CI = 0.01 , 2.21 ) ] . Interactions with sex show stronger associations for females than males in young adulthood [ e.g. V‐HYS  : CUD × sex interaction on psychotic symptoms significant after age 26 ( b = 1.12 , 95 % CI = 0.02 , 2.21 ) ] . Findings were not moderated by early‐onset CU . Conclusions Significant associations between cannabis use ( CU ) frequency and disorder ( CUD ) and psychotic and depressive symptoms in late adolescence and young adulthood extend across adulthood , and include anxiety Cannabidiol ( CBD ) , a major phytocannabinoid constituent of cannabis , is attracting growing attention in medicine for its anxiolytic , antipsychotic , antiemetic and anti-inflammatory properties . However , up to this point , a comprehensive literature review of the effects of CBD in humans is lacking . The aim of the present systematic review is to examine the r and omized and crossover studies that administered CBD  to healthy controls and to clinical patients . A systematic search was performed in the electronic data bases PubMed and EMBASE using the key word “ cannabidiol ” . Both monotherapy and combination studies ( e.g. , CBD + ∆9-THC ) were included . A total of 34 studies were identified : 16 of these were experimental studies , conducted in healthy subjects , and 18 were conducted in clinical population s , including multiple sclerosis ( six studies ) , schizophrenia and bipolar mania ( four studies ) , social anxiety disorder ( two studies ) , neuropathic and cancer pain ( two studies ) , cancer anorexia ( one study ) , Huntington ’s disease ( one study ) , insomnia ( one study ) , and epilepsy ( one study ) . Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC . Moreover , some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and /or intensify ∆9-THC-induced effects , whereas others suggest that it may inhibit ∆9-THC-induced effects . Finally , preliminary clinical trials suggest that high-dose oral CBD ( 150–600 mg/d ) may exert a therapeutic effect for social anxiety disorder , insomnia and epilepsy , but also that it may cause mental sedation . Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed Previous studies have suggested that marijuana ( cannabis sativa ) and delta-9-tetrahydrocannabinol ( delta9-THC ) , the major psychoactive ingredient of marijuana , are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome ( TS ) . Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users , we performed a r and omized double-blind placebo-controlled crossover trial for delta9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of delta9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance . Using a variety of neuropsychological tests , we found no significant differences after treatment with delta9-THC compared to placebo treatment in verbal and visual memory , reaction time , intelligence , sustained attention , divided attention , vigilance , or mood . Only when using the Symptom Checklist 90-R ( SCL-90-R ) did our data provide evidence for a deterioration of obsessive-compulsive behavior ( OCB ) and a trend towards an increase in phobic anxiety . However , these results should be interpreted with caution as SCL-90-R has known limitations on measuring OCB . We suggest that the increase in phobic anxiety is mainly due to the fact that a single-dose treatment rules out the possibility of administering the dosage slowly . In contrast to results obtained from healthy marijuana users , a single-dose treatment with delta9-THC in patients suffering from TS does not cause cognitive impairment . We therefore suggest that further investigations should concentrate on the effects of a longer-term therapy of TS with delta9-THC BACKGROUND Cannabis use is common in patients with bipolar disorder , however little is known about cannabis as a risk factor for mania . In order to investigate the association between exposure to cannabis and subsequent development of manic symptoms whilst controlling for psychotic symptoms , a longitudinal population -based study was carried out . METHODS 4815 individuals aged 18 to 64 years were interviewed using the Composite International Diagnostic Interview at baseline , 1 year follow up and 3 year follow up , including assessment of substance use , manic symptoms and psychotic symptoms . RESULTS Use of cannabis at baseline increased the risk for manic symptoms during follow-up ( adjusted OR 2.70 , 95 % CI : 1.54 , 4.75 ) , adjusted for age , sex , educational level , ethnicity , single marital status , neuroticism , use of other drugs , use of alcohol , depressive symptoms and manic symptoms at baseline . The association between cannabis use and mania was independent of the prevalence and the incidence of psychotic symptoms . There was no evidence for reverse causality , as manic symptoms at baseline did not predict the onset of cannabis use during follow-up ( OR = 0.35 , 95 % CI : 0.03 , 3.49 ) . LIMITATIONS As 3 years is a relative short period of follow-up , long-term effects of cannabis use on mania outcomes could not be detected . CONCLUSION The results suggest that cannabis use may affect population expression of manic symptoms ( and subsequent risk to develop bipolar disorder [ Regeer , E.J. , Krabbendam , L. , R , DE Graaf , Ten Have , M. , Nolen , W.A. , Van Os , J. , 2006 . A prospect i ve study of the transition rates of subthreshold (hypo)mania and depression in the general population . Psychol Med , 1 - 9 . ] ) . These findings may not be due to the emergence of psychotic symptoms or the effects of self-medication Background : Chronic neuropathic pain affects 1%–2 % of the adult population and is often refractory to st and ard pharmacologic treatment . Patients with chronic pain have reported using smoked cannabis to relieve pain , improve sleep and improve mood . Methods : Adults with post-traumatic or postsurgical neuropathic pain were r and omly assigned to receive cannabis at four potencies ( 0 % , 2.5 % , 6 % and 9.4 % tetrahydrocannabinol ) over four 14-day periods in a crossover trial . Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle , followed by a nine-day washout period . Daily average pain intensity was measured using an 11-point numeric rating scale . We recorded effects on mood , sleep and quality of life , as well as adverse events . Results : We recruited 23 participants ( mean age 45.4 [ st and ard deviation 12.3 ] years , 12 women [ 52 % ] ) , of whom 21 completed the trial . The average daily pain intensity , measured on the 11-point numeric rating scale , was lower on the prespecified primary contrast of 9.4 % v. 0 % tetrahydrocannabinol ( 5.4 v. 6.1 , respectively ; difference = 0.7 , 95 % confidence interval [ CI ] 0.02–1.4 ) . Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief . Participants receiving 9.4 % tetrahydrocannabinol reported improved ability to fall asleep ( easier , p = 0.001 ; faster , p < 0.001 ; more drowsy , p = 0.003 ) and improved quality of sleep ( less wakefulness , p = 0.01 ) relative to 0 % tetrahydrocannabinol . We found no differences in mood or quality of life . The most common drug-related adverse events during the period when participants received 9.4 % tetrahydrocannabinol were headache , dry eyes , burning sensation in areas of neuropathic pain , dizziness , numbness and cough . Conclusion : A single inhalation of 25 mg of 9.4 % tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain , improved sleep and was well tolerated . Further long-term safety and efficacy studies are indicated . ( International St and ard R and omised Controlled Trial Register no. IS RCT N68314063 BACKGROUND Patients who experience the onset of psychotic illness with a comorbid diagnosis of cannabis dependence experience poor clinical outcomes . Few studies have identified interventions that reduce cannabis use and improve clinical outcome in this population . AIMS We undertook a multi-center , r and omized controlled trial of a group psychological intervention for psychosis with comorbid cannabis dependence to determine whether there was any impact on cannabis use symptoms , global functioning , insight , attitudes to treatment and subjective quality of life . METHOD Across three centers , we compared a group psychological intervention , based on cognitive behavioral therapy and motivational interviewing , with treatment as usual among patients experiencing their first psychotic episode or early in the course of psychotic illness . Substance misuse and indices of clinical outcome were assessed at baseline , 3months and 1year . RESULTS At 3month and 1year follow-ups , there was no evidence for an intervention effect on cannabis use , symptoms , global functioning insight or attitude to treatment . However , the intervention improved subjective quality of life at 3months and this effect was sustained at 1year . CONCLUSIONS Over the early phase of psychotic illness , group psychological interventions for those with comorbid cannabis dependence improved subjective quality of life . However , this was not associated with reduction in use of cannabis or improvement in clinical outcomes 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 BACKGROUND There are inconsistencies in findings as to whether cannabis use has a negative impact on clinical outcomes for people with established psychosis . Effects may be more evident on patients with recent onset psychosis . AIM To investigate the relationship between cannabis use and clinical outcome , including whether change in cannabis use affects psychotic symptoms , affective symptoms , functioning and psychotic relapse in a sample of people in early psychosis with comorbid cannabis abuse or dependence . METHODS One hundred and ten participants were examined prospect ively with repeated measures of substance use antecedent to psychopathology at baseline , 4.5 , 9 , and 18 months . We used r and om intercept models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS There was no evidence of a specific association between cannabis use and positive symptoms , or negative symptoms , relapse or hospital admissions . However , a greater dose of cannabis was associated with subsequent higher depression and anxiety . Change in the amount of cannabis used was associated with statistically significant corresponding change in anxiety scores , but not depression . Additionally , reductions in cannabis exposure were related to improved patient functioning . CONCLUSIONS Reducing cannabis may be directly associated with improvements in anxiety and functioning , but not other specific symptoms Community-based studies suggest that cannabis products that are high in Δ9-tetrahydrocannabinol ( THC ) but low in cannabidiol ( CBD ) are particularly hazardous for mental health . Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form , under controlled conditions . In a between-subjects design , we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment . Healthy participants were r and omised to receive oral CBD 600 mg ( n=22 ) or placebo ( n=26 ) , 210 min ahead of intravenous ( IV ) THC ( 1.5 mg ) . Post-THC , there were lower PANSS positive scores in the CBD group , but this did not reach statistical significance . However , clinical ly significant positive psychotic symptoms ( defined a priori as increases ≥3 points ) were less likely in the CBD group compared with the placebo group , odds ratio (OR)=0.22 ( χ2=4.74 , p<0.05 ) . In agreement , post-THC paranoia , as rated with the State Social Paranoia Scale ( SSPS ) , was less in the CBD group compared with the placebo group ( t=2.28 , p<0.05 ) . Episodic memory , indexed by scores on the Hopkins Verbal Learning Task-revised ( HVLT-R ) , was poorer , relative to baseline , in the placebo pre-treated group ( -10.6±18.9 % ) compared with the CBD group ( -0.4%±9.7 % ) ( t=2.39 , p<0.05 ) . These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health OBJECTIVE We sought to examine the relation between cannabis abuse and the symptomatic course of recent-onset schizophrenia and related disorders . DESIGN A prospect i ve cohort study over a year using monthly Brief Psychiatric Rating Scale assessment s. PARTICIPANTS  Cannabis-abusing patients ( n = 24 ) were compared with nonabusers ( n = 69 ) . Eleven patients were mild and 13 were heavy cannabis-abusing patients . RESULTS Significantly more and earlier psychotic relapses occurred in the cannabis-abusing group ( P = .03 ) . This association became stronger when mild and heavy cannabis abuse were distinguished ( P = .002 ) . No confounding effect of other variables , eg , other street drugs , was found . In all but one patient , cannabis abuse preceded the onset of the first psychotic symptoms for at least 1 year . CONCLUSIONS Cannabis abuse and particularly heavy abuse can be considered a stressor eliciting relapse in patients with schizophrenia and related disorders and possibly a premorbid precipitant
INTERPRETATION A single THC administration induces psychotic , negative , and other psychiatric symptoms with large effect sizes .
There is no consistent evidence that CBD induces symptoms or moderates the effects of THC .
BACKGROUND Approximately 188 million people use cannabis yearly worldwide , and it has recently been legalised in 11 US states , Canada , and Uruguay for recreational use .
The potential for increased cannabis use highlights the need to better underst and its risks , including the acute induction of psychotic and other psychiatric symptoms .
We aim ed to investigate the effect of the cannabis constituent Δ9-tetrahydrocannabinol ( THC ) alone and in combination with cannabidiol ( CBD ) compared with placebo on psychiatric symptoms in healthy people .