There is increased risk of psychosis associated with cannabis use disorder and the interaction of THC with dopamine neurotransmission is complex. It is important to investigate the recovery from cannabis-induced psychosis and its effects on the brain’s dopamine neurotransmission. This study was to evaluate dopamine receptor D2 availability in the striatum (caudate/putamen) in recently abstinent cannabis dependent users after recovery from psychosis in comparison with abstinent MDMA “ecstasy” abusers and healthy control participants. Participants were eight abstinent ex cannabis-dependent users who were treated for cannabis-induced psychosis with anti-psychotic medication and psychosocial support for 4 months in an inpatient treatment center for drug users. They were compared with nine abstinent ex MDMA “ecstasy” abusers who received medication and psycho-social treatment for 4 months at the same treatment facility and eight healthy control participants. All participants were scanned with bolus and constant infusion of [123I] Iodobenzamide (IBZM) in Single Photon Computed Tomography (SPECT). Cannabis abstinent users who were treated for cannabis-induced psychotic episodes showed no difference in dopamine D2 receptor availability in the caudate compared with abstinent MDMA “ecstasy” abusers and healthy control participants. This finding indicates minimal effects of cannabis-induced psychosis on dopamine reward mechanisms. There is evidence for reduced D2 receptor availability measures in the right putamen (uncorrected) which may indicate a residual effect of anti-psychotic medication. Cannabis abstinent users who were treated for cannabis-induced psychotic episodes showed no difference in dopamine D 2 receptor availability in the caudate compared with abstinent MDMA “ecstasy” abusers and healthy control participants. This finding indicates minimal effects of cannabis-induced psychosis on dopamine reward mechanisms. There is evidence for reduced D 2 receptor availability measures in the right putamen (uncorrected) which may indicate a residual effect of anti-psychotic medication. Regular cannabis users after abstinence and recovery display dopamine D 2 measures of availability that is not different from healthy control participants ( 25–27 ). These findings indicate normal levels of dopamine function after recovery. However, recovery as result of treatment cannot be ascertained because baseline measures of dopamine D 2 availability were not taken in these studies. Furthermore, it is not The increased risk of cannabis-induced psychosis and the complex interaction of THC with dopamine neurotransmission, merits an investigation on the effects of cannabis-induced psychosis on the brain’s dopamine neurotransmission mechanisms after recovery. Previous studies have investigated the relationship between striatal dopamine function and symptoms in psychotic disorders, and they have measured the whole striatum ( 28–30 ). Abstinent cannabis users who recovered from cannabis-induced psychosis The group consisted of eight cannabis-dependent users, six males and two females with mean age 23 years and 4 months (S.D = 1.03) fulfilling DSM-IV ( 32 ) with diagnosis of substance-induced psychotic disorder (SIPD). They were treated with anti-psychotic medication and psychosocial support for 4 months in an inpatient treatment center. Their psychosis lasted on average for 1 month (S.D = 0.53). All participants used cannabis regularly before their psychosis. Abstinent cannabis users recovered from psychosis Abstinent MDMA “ecstasy” abusers Healthy Control participants Comparison between abstinent cannabis users and control participants Number and frequencies (male: female) 8 (6:2) 9 (8:1) 8 (7:1) n.s. Age- mean (S.D) 23.3 (1.03) 25 (3.5) 35.75 (6.5) t (1,7) = 5.77; p = 0.001. Healthy control participants The control group consisted of eight healthy drug-free (based on self-report) participants, seven males and one female with mean age 35 years and 9 months (S.D = 6.5). They took part in our earlier study ( 33 ) and underwent the same recruitment and assessment procedure as the main group of cannabis users who recovered from cannabis-induced psychosis and the same imaging procedure in the same scanner SPECT (Hawkeye, GE Healthcare). Cannabis use interacts with the dopamine catechol-O-methyl transferase (COMT) Val158Met polymorphism ( 56 ). Finally, regular cannabis use exacerbated the symptoms among recent onset cases of schizophrenia ( 57 , 58 ). However, most cannabis users do not develop schizophrenia. Cannabis may initiate psychotic symptoms in individuals with genetic vulnerability and family history of mental illness, and this may cause concern among healthcare professionals. We report the first study to the best of our knowledge that has assessed dopamine D 2 receptor availability in abstinent cannabis dependent individuals who recovered from cannabis-induced psychosis. Finally, there is evidence that rTMS can be effective in the treatment of addiction, with promising results in treatment of cocaine, and cannabis use disorder ( 71 ). Future studies could examine the use of rTMS in treatment of patients with cannabis use disorder and those with cannabis-induced psychosis. Limitations First, this study is a cross-sectional study hence it is not possible to ascertain directly recovery from cannabis induced psychosis and the effects of medication on the brain’s dopamine D 2 receptor availability. Finally, this was a relatively small sample of participants due to major difficulties recruiting and scanning patients who were treated for cannabis-induced psychosis and “ecstasy” abusers. According to our power calculations 15 participants in each group would be required in order to provide definite results. Unfortunately, most studies that measured dopamine occupancy in cannabis use disorder have used a smaller number of participants which is a limitation in these kind of studies due to recruitment issues.

RATIONALE To date, the exposure to Synthetic Cannabinoids (SCs) has been linked to unanticipated psychiatric symptoms such as agitation, psychosis, and aggressive behavior. In line with this, preclinical studies have shown that acute and long-term exposure to these compounds can result in psychostimulant effects that may be related to CB1-mediated and dopamine-dependent mechanisms. OBJECTIVES This study focuses on the progressive effects induced by repeated injection of 1-pentyl-3-(1-naphthoyl)indole JWH-018 (6 mg/kg, i.p.) on the locomotor activity and aggressive behavior in adult male ICR-CD1® mice. Thus, the interaction with the cannabinoid CB1 receptor-preferring antagonist/inverse agonist AM-251 (6 mg/kg, i.p.), the dopamine D1/5 receptor antagonist SCH23390 (0.1 mg/kg, i.p.), and the dopamine D2/3 receptor antagonist haloperidol (0.05 mg/kg, i.p.) have been evaluated. Expression and distribution of D1 and D2 receptors and tyrosine hydroxylase (TH) have been also investigated by immunohistochemistry on brain and cerebellar samples to explore potential neuroplastic events. RESULTS The repeated treatment with JWH-018 lead to the exacerbation of unanticipated psychomotor agitation, progressively increasing spontaneous locomotion and aggressiveness. Pre-treatment with AM-251 prevents the effects induced by the SC first, third and seventh injection. SCH23390 and haloperidol significantly attenuate and fully prevent the effects induced by JWH-018 seventh injection when pre-administered, respectively, alone and in combination. Behavioral changes observed in JWH-018-treated mice are accompanied by alterations in cortical, hippocampal, striatal and cerebellar D1, D2 and TH gene expression levels. CONCLUSION The present results demonstrated that repeated treatment with high dosage of JWH-018 induces psycho-stimulants effects via both CB1 receptor-mediated and dopamine-dependent mechanisms.

Although cannabis use may be involved in the aetiology of acute psychosis, there has been considerable debate about the association observed between cannabis use and chronic psychosis. In particular, because of the frequent co-occurrence between schizophrenia and cannabis use, the question has been raised of a causal link between exposure to cannabis as a risk factor and the development of psychosis or psychotic symptoms.The aim of this article was to examine the evidence that cannabis use causes chronic psychotic disorders by using established criteria of causality. These criteria were defined by: biologic plausibility, strength of the interaction between the risk factor and the disease, reprieability of the results, temporal sequence between the exposure to the risk factor and the beginning of the disease and existence of a dose-effect relationship.The selected studies were found in Medline using the keywords "cannabis" and "psychosis", "cannabis" and "schizophrenia", "cannabis" and "psychotic symptoms" and "prospective" or "cohort" or "longitudinal". The selected studies were all prospective studies assessing the temporal sequence between cannabis use and emergence of psychosis or psychotic symptoms. The search strategies resulted in 60 records that were screened by reading both titles and abstracts. Seventeen studies were considered eligible, and then, after reading the full text, seven met the inclusion criteria.Together, the seven studies were all prospective cohorts an

The legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabinoids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or synthetized cannabinoids-often used as adjuvants to standard medicines-may produce small to modest benefits. This is primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and other medical conditions. Safety: Cannabis-based medicine is generally well Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Overdosing and unintentional cannabis use may cause short term psychiatric, gastrointestinal, and cardiovascular problems in children, teens, and adults [ 22 , 23 ]. These unpleasant symptoms generally subside without the need for medical assistance but can require medical assistance in more severe cases. Motoric incoordination Acute cannabis consumption has consistently been associated with a modest increase in the risk of traffic accidents, with odd ratios ranging from 1.25 to 1.97 [ 17 ]. The causal pathways and mechanisms underlying the association between cannabis use, cannabis use disorder and anxiety or mood disorders remain unclear [ 40 ]. Psychotic disorders Meta-analyses of case–control and cohort studies report a robust association between cannabis use and the risk of a psychotic disorder, and a dose–response relationship between this risk and the frequency of cannabis use [ 16 ]. A multinational study in Europe and Brazil [ 50 ] found that daily use of high potency cannabis increased the risk of psychosis fivefold compared to non-users while daily use of low potency cannabis doubled the risk. Use less than once a week was not associated with a psychotic disorder risk (other than acute psychoses which can emerge even with first time consumption of high THC doses). The prevalence of daily cannabis use and high potency cannabis use was positively associated with the incidence of treated psychosis across study sites in Europe and Brazil. More recently, a study based on electronic record over 5 decades in the Danish population reported an increase in the incidence of schizophrenia associated with use of THC and CUD, predominantly among young males 20–30 years of age in whom cannabis use accounted for 30% of the cases [ 51 ]. They affect vasculature and myocardium directly via specific receptors and exert indirect effects through the central and peripheral nervous system. THC acutely stimulates the cardiovascular system, increases heart rate and produces a change in blood pressure. This occurs primarily due to sympathetic nervous system activation and parasympathetic nervous system inhibition [ 68 ]. There are case reports of adverse cardiovascular risks in chronic cannabis users (e.g., myocardial infarctions, tachycardia, dysrhythmias, hypotension, and orthostatic hypotension) [ 68 – 70 ]. The endogenous cannabinoid system may also provide an array of potential benefits, particularly in the role of CBD as a neuroprotector for stroke [ 73 ]. Rigorous studies supporting these positive effects are missing [ 72 ]. Hyperemesis syndrome Cannabis can cause recurring bouts of nausea, vomiting and intense abdominal pain amidst other acute gastrointestinal symptoms that are severe enough to prompt users to seek medical help [ 23 ]. These cyclical episodes occur with prolonged, high-dose cannabis

Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs.

as schizophrenia) are associated in the general population 1 , 2 , and heavy cannabis users are over-represented among new cases of schizophrenia 3 - 5 ,. These findings, and rising rates of cannabis use among young people in many developed countries, have prompted debates about whether cannabis use may be a contributory cause of psychosis, that is, it may precipitate schizophrenia in vulnerable individuals. This hypothesis assumes that cannabis use is one factor among many others (including genetic predisposition and other unknown causes) that together cause schizophrenia. There are also other possible explanations of the association. Common factors may increase the risk of cannabis use and psychosis, without the two being directly related. Cannabis could also be used to self-medicate the symptoms of schizophrenia 6 - 15 . The consistent finding of an association between cannabis use and psychosis makes chance an unlikely explanation of the association, and there are also now a number of prospective studies showing that cannabis use often precedes psychosis. The more difficult task has been excluding the hypothesis that the relationship is due to other factors, such as other drug use or a genetic predisposition to develop schizophrenia and use cannabis. LONGITUDINAL STUDIES The strongest evidence that cannabis use is a contributory cause of schizophrenia comes from longitudinal studies of large representative samples of the population who have been followed over time to see if cannabis users are at higher risk of developing schizophrenia. The earliest such study was a 15-year prospective investigation of cannabis use and schizophrenia in 50,465 Swedish conscripts. The study found that those who had tried cannabis by age 18 were 2.4 times more likely to be diagnosed with schizophrenia than those who had not 16 and the risk of this diagnosis increased with the frequency of cannabis use. The risks were substantially reduced but still significant after statistical adj doi: 10.1002/j.2051-5545.2008.tb00158.x Cannabis use and the risk of developing a psychotic disorder WAYNE HALL WAYNE HALL 1 School of Population Health, University of Queensland, Herston Road, Herston QLD 4006, Australia Find articles by WAYNE HALL 1 , LOUISA DEGENHARDT LOUISA DEGENHARDT 2 National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052, Australia Find articles by LOUISA DEGENHARDT 2 Author information Copyright and License information 1 School of Population Health, University of Queensland, Herston Road, Herston QLD 4006, Australia 2 National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052, Australia World Psychiatric Association PMC Copyright notice PMCID: PMC2424288  PMID: 18560513 Abstract We briefly review the evidence that cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychoses, by summarising longitudinal studies that: a) have examined relationships between cannabis use and the risk of psychosis or psychotic symptoms; and b) have controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We briefly explore the clinical and public health implications of the most plausible hypothesis, that cannabis use precipitates schizophrenia in persons who are vulnerable because of a personal or family history of schizophrenia. Keywords: Cannabis, psychosis; schizophrenia; adolescents; dopamine; educational interventions Regular cannabis use and psychotic disorders (such as schizophrenia) are associated in the general population 1 , 2 , and heavy cannabis users are over-represented among new cases of schizophrenia 3 - 5 ,. These findings, and rising rates of cannabis use among young people in many developed countries, have prompted debates about whether cannabis use may be a contributory cause of psychosis, that is, it may precipitate schizophrenia in vulnerable individuals. This hypothesis assumes that cannabis use is one factor among many others (including genetic predisposition and other unknown causes) that together cause schizophrenia. There are also other possible explanations of the association. Common factors may increase the risk of cannabis use and psychosis, without the two being directly related. Cannabis could also be used to self-medicate the symptoms of schizophrenia 6 - 15 . The consistent finding of an association between cannabis use and psychosis makes chance an unlikely explanation of the association, and there are also now a number of prospective studies showing that cannabis use often precedes psychosis. The more difficult task has been excluding the hypothesis that the relationship is due to other factors, such as other drug use or a genetic predisposition to develop schizophrenia and use cannabis. Assuming a causal relationship, and given current patterns of use, they estimated that Mannisto P, Kaakkola S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev. 2006;51:593–628. [ PubMed ] [ Google Scholar ] 38. Hall WD, Degenhardt L. Is there a specific ‘cannabis psychosis’? In: Castle DJ, Murray RM, editors. Marijuana and madness. Cambridge: Cambridge University Press; 2004. pp. 89–100. [ Google Scholar ] 39. Degenhardt L, Tennant C, Gilmour S. The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: findings from a 10-month prospective study. Psychol Med. 2007;37(Suppl. 18):927–934. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325:1195–1198. doi: 10.1136/bmj.325.7374.1195. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 53. Hall WD, Degenhardt L. What are the policy implications of the evidence on cannabis and psychosis? Can J Psychiatry. 2006;51:566–574. doi: 10.1177/070674370605100904.

between psychosis and cannabis is controversial because observational studies suggest a correlation but do not establish any causative effect of cannabis on The long-term effects of cannabis have been the subject of ongoing debate. Given that the use of cannabis is illegal in most countries, clinical research presents a challenge and there is limited evidence from which to draw conclusions. In 2017, the U.S. National Academies of Sciences, Engineering, and Medicine issued a report summarizing much of the published literature on health effects of canna pers…

Active constituents of Cannabis lead to positive or negative symptoms. Some of them are: decreased activity for life, inability to overcome adversities, stupefaction, confusion, hallucination and fear with attacks of panic (psychosis), passivity, apathy, fatigue, flight of ideas, concentration disorder, attention disorder, lack of time sense. Activity of THC lasts longer than it is measured in body fluids. Personal feelings which affect the smoker are very hard to define. THC is also the compound which causes great analytical and interpretative problems. It interacts with organism at low doses, which produce extremely low concentrations in body fluid. This refers to THC and its metabolites produced by fast metabolism mechanism. THC and its major metabolite (11-OH-THC) are psychoactive, second metabolite (THCCOOH) is inactive. Both THC and 11-OH-THC are eliminated from the organism very fast. On the other side THCCOOH is being cumulated. Presence of one, two or three compounds in different kinds of body fluids collected form Cannabis consumers (mainly smokers) has various value for interpretation whether the consumer is or is not under the influence of THC, which is important from the legal point of view. Main reason to conduct this research was to establish a method for simultaneous detection and determination of THC and its two major metabolites - 11-OH-THC and THCCOOH in body fluids, and afterwards to verify it according to international standards. Full characterization of

2025-04-03. Pearson, Nathan T.; Berry, James H. (2019-10-28). "Cannabis and Psychosis Through the Lens of DSM-5". International Journal of Environmental Research Synthetic Cannabinoid Use Disorder (SCUD) is a psychiatric condition characterised by the rise of significant health problems from the continued use of synthetic cannabinoids (otherwise known as 'Spice' or 'K2'). Synthetic cannabinoids are artificially modified chemicals that imitate the effects of delta-9-tetrahydrocannabinol, the main psychoactive compound in cannabis. Symptoms of SCUD include h Synthetic cannabinoid use disorder is characterised by the hyper-activation of CB1 receptors, as synthetic cannabinoids act as agonists with a stronger binding affinity than natural cannabis. Cannabinoid receptors are extensively distributed everywhere in the body, but especially in brain regions responsible for functions such as memory, movement and emotion. Activation of these receptors changes the way signals are sent between nerve cells in the brain and other parts of the body, influencing both excitatory and inhibitory synaptic transmission by reducing neurotransmitter release in the synaptic cleft. Additionally, synthetic cannabinoids interfere with neurogenesis-related processes and brain-derived neurotrophic factor expression, disrupting endocannabinoid homeostasis. This dysregulation then manifests as physiological symptoms of SCUD, where the location of CB1 receptor activation correlates with specific health complications. An example would be the activation of CB1 receptors in bronchial smooth muscles, which consequently triggers airway constriction, interfering with gas exchange and inducing respiratory depression. Synthetic cannabinoids exhibit cross-reactivity with non-cannabinoid receptors due to structural similarities. Hyper-activation of CB1 receptors on GABAergic interneurons in the ventral tegmental area reduces GABA release onto dopaminergic neurons. While not only reinforcing drug-seeking behaviour through increasing tonic dopamine release in the nucleus accumbens, GABAergic inhibition also plays a significant role in maintaining and lowering an individual's seizure threshold. Furthermore, synthetic cannabinoids mimic serotonin at 5-HT receptors, triggering serotonin syndrome. Serotonin syndrome can lead to anxiety, psychosis and perceptual distortions through amplified glutamatergic activity in the prefrontal cortex. Certain metabolites of synthetic cannabinoids are known to exhibit toxic effects by influencing cannabinoid receptor activity. Some metabolites derived from synthetic cannabinoids such as JWH-018 retain or increase CB1 receptor affinity, extending the psychotropic and physiological effects of the drug. Neuroadaptations and…