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Cannabis

A widely used plant studied across pain, anxiety, sleep, and its interactions with mental health.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Cannabis, marijuana, THC, cannabidiol, CBD, then ranked by relevance.

The research indicates that cannabis use is associated with an increased risk of psychotic symptoms and disorders, with controlled laboratory studies showing that cannabinoid agonists can transiently produce schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in those with schizophrenia. However, the evidence is complicated by high rates of polysubstance use, and the long-term effects and mechanisms remain areas of active investigation. The findings are consistent across multiple study types, but the overall confidence is limited by the prevalence of observational designs and the confounding factor of co-use with other substances.

Confidence in the evidence

Low-Moderate
  • The evidence includes controlled laboratory studies (RCTs) showing a causal link between cannabinoid agonists and transient psychotic symptoms, but these are acute effects and not necessarily indicative of long-term risk.
  • Observational and review studies consistently report an association between cannabis use and psychosis, but these are limited by confounding factors like polysubstance use and lack of blinding.
  • The sample sizes in the most direct experimental studies are not reported in the abstracts, and the overall body of evidence is heterogeneous in design and population.
  • There is a lack of large-scale, long-term prospective studies that adequately control for confounds, reducing the ability to draw firm causal conclusions.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. 2018
Unclear

This comprehensive review describes the ethnopharmacology and pharmacology of Cannabis sativa, including its key psychoactive constituent THC and the endocannabinoid system, but does not directly assess clinical outcomes.

review

Human Laboratory Studies on Cannabinoids and Psychosis. 2016
Supports

Controlled laboratory studies demonstrate that cannabinoid agonists produce positive, negative, and cognitive symptoms resembling schizophrenia in healthy subjects and transiently exacerbate symptoms in individuals with schizophrenia, challenging the self-medication hypothesis.

review of RCTs

Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light 2011
Supports

This review discusses evidence that cannabis, among other drugs, can induce schizophrenia-like psychosis, contributing to the view that liability to psychosis is continuously distributed in the population.

review

Substance-Induced Psychoses: An Updated Literature Review 2021
Supports

This updated review finds that abuse of cannabis plays a significant role in increasing the incidence of episodes resembling a psychotic disorder, though it notes the difficulty in distinguishing induced psychosis from primary psychotic disorders due to frequent comorbidity.

narrative review

Functional recovery trajectories in cannabis-induced first-episode psychosis: The role of dissociative symptoms in the discrepancy between symptomatic improvement and functional outcomes. 2026
Supports

In a 24-month prospective study of 72 patients with cannabis-induced first-episode psychosis, continued cannabis use was associated with worse functional outcomes, with dissociative symptoms mediating 35% of this effect.

prospective cohort Sample size: 72

Drug models of schizophrenia. 2015
Unclear

This review selectively examines findings from cannabinoid pharmacological drug models to evaluate their similarity to schizophrenia, but does not provide a specific directional finding on cannabis itself.

review

A Clinical and Metabolic Study of Acute Intoxication with Cannabis Sativa and its Role in the Model Psychoses 1958
Unclear

This historical study describes the effects of oral cannabis administration and its potential as a model psychosis, but the abstract does not provide specific quantitative results.

clinical study

The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview 2006
Mixed

This review notes that cannabis use is a well-recognized risk factor for neuropsychiatric disorders and contributes to psychological problems in ecstasy users, but also that cannabinoids have neuroprotective actions that may partially block MDMA-induced neurotoxicity in animals.

review

MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress 2006
Mixed

This review states that around 90-95% of ecstasy/MDMA users also take cannabis, which can independently contribute to adverse neuropsychobiological profiles, though acute co-use may be interactive rather than additive due to cannabis's relaxant and hypothermic properties.

review

Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) 2000
Supports

This study raises concern that use of ecstasy, possibly in conjunction with cannabis, may lead to cognitive decline in otherwise healthy young people, suggesting an impairment of working memory.

observational

Patterns of simultaneous polysubstance use in drug using university students 2006
Unclear

This study found that cannabis is frequently co-administered with alcohol, tobacco, and other substances, but patterns of cannabis use were not systematically related to other substances administered.

observational Sample size: 149

Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. 2012
Unclear

This review discusses synthetic cannabinoids (e.g., K2, Spice) as herbal marijuana alternatives, noting their adverse effects ranging from minimal to life-threatening, but does not directly address cannabis itself.

review

Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). 2010
Unclear

This in vitro study found that THC inhibits human P-glycoprotein and breast cancer resistance protein in a concentration-dependent manner, suggesting potential drug-drug interactions, but does not assess clinical outcomes.

in vitro

Medicinal Plants with Psychoactive Properties: A Comprehensive Review 2026
Unclear

This review includes Cannabis sativa among 20 medicinal plants with psychoactive properties, noting its neuropharmacological activities through modulation of the endocannabinoid system, but does not provide specific clinical findings.

review

Cannabis Sativa, religion and society: Historical, medicinal, legal, and sacramental perspectives 2026
Unclear

This article examines the historical, medicinal, legal, and religious aspects of Cannabis sativa, but does not present empirical findings on health outcomes.

review

Prophylactic efficacy of cannabidiol and sodium nitroprusside in a ketamine model of schizophrenia: sex-dependent effects on positive-like and cognitive impairments 2026
Mixed

In a rodent model of schizophrenia, cannabidiol (CBD) combined with sodium nitroprusside showed prophylactic efficacy in preventing ketamine-induced positive-like and cognitive impairments, with sex-dependent effects, but CBD alone had limited efficacy.

preclinical (animal study)

Psychedelic-Assisted Psychotherapy for the Treatment of PTSD: A Systematic Review and Meta-Analysis 2026
No effect

In a meta-analysis of 11 RCTs for PTSD, a single cannabidiol trial showed no clear benefit, while MDMA-assisted psychotherapy showed a significant moderate-to-large reduction in PTSD symptom severity.

systematic review and meta-analysis Sample size: 358

Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada 2013
Unclear

This study found that ayahuasca-assisted therapy was associated with improvements in factors related to problematic substance use, but does not directly address cannabis.

observational

Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey 2020
Unclear

This survey found persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use, but the cross-sectional design cannot determine causality.

cross-sectional survey

Standardised Mindfulness-Based Interventions in Healthcare: An Overview of Systematic Reviews and Meta-Analyses of RCTs 2015
Unclear

This review found that mindfulness-based interventions improved depressive symptoms, anxiety, stress, quality of life, and physical functioning, but does not address cannabis.

systematic review and meta-analysis Sample size: 8683

A cross-national comparison of nonmedical and medical use of psychedelic drugs in the international cannabis policy study. 2026
Unclear

This study estimated prevalence of psychedelic use and medical discussions, but does not directly address cannabis.

cross-sectional survey

The need for another tool: Australian healthcare professionals on the use of psilocybin for existential distress in people with cancer 2026
Unclear

This qualitative study explored healthcare professionals' attitudes toward psilocybin-assisted therapy for existential distress in cancer patients, but does not address cannabis.

qualitative Sample size: 11

Past-Year Psilocybin and Alcohol Co-Use: Associations With Mental Health Symptoms 2026
Unclear

This study found that individuals with past-year psilocybin and alcohol co-use had fewer depressive symptoms than those who used alcohol without psilocybin, but does not directly address cannabis.

cross-sectional survey Sample size: 2841

Attitudes of Mental Healthcare Professionals Towards the Use of Psychedelics in the Treatment of Substance Use Disorders: A Systematic Review 2026
Unclear

This systematic review found that mental healthcare professionals hold cautiously optimistic attitudes toward psychedelic-assisted therapy for substance use disorders, but does not directly address cannabis.

systematic review Sample size: 966

Spiritual health and healing in Ethiopia: A scoping review and thematic analysis of beliefs, practices, and gaps in healthcare integration 2026
Unclear

This scoping review maps spiritual health beliefs and practices in Ethiopia, but does not address cannabis.

scoping review

Points of agreement

  • Multiple reviews and controlled laboratory studies converge on the finding that cannabinoid agonists can induce transient psychotic-like symptoms in healthy individuals and exacerbate symptoms in those with schizophrenia.
  • Observational studies consistently report an association between cannabis use and increased risk of psychotic disorders, though causality is difficult to establish due to confounding factors.
  • The evidence suggests that cannabis use is a significant environmental factor in the development of psychosis, particularly in vulnerable individuals.

Conflicts

  • There is a conflict between the potential neuroprotective effects of cannabinoids (e.g., blocking MDMA-induced neurotoxicity in animal studies) and the observed adverse neuropsychiatric effects in human observational studies.
  • The role of cannabis in cognitive decline is debated, with some studies suggesting impairment while others note that effects may be confounded by polysubstance use.
  • The self-medication hypothesis for cannabis use in schizophrenia is challenged by laboratory studies showing exacerbation of symptoms, but observational data cannot fully rule it out.

Gaps

  • Long-term prospective studies with adequate control for polysubstance use are lacking, making it difficult to isolate the specific effects of cannabis on psychosis and cognition.
  • The durability of cannabis-induced psychotic symptoms and the long-term functional outcomes in patients with cannabis-induced psychosis are not well characterized.
  • There is a need for more research on the dose-response relationship and the differential effects of various cannabinoids (e.g., THC vs. CBD) on mental health outcomes.
  • The role of genetic vulnerability (e.g., COMT, DAT1 polymorphisms) in moderating the effects of cannabis on psychosis is underexplored in large-scale studies.
  • Most studies focus on acute or short-term effects; the long-term neurobiological and cognitive consequences of chronic cannabis use remain poorly understood.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Cannabis, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Cannabis or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: June 2026 →

1,011 articles · 251 from the last two years · 3,395,243 participants across 466 studies reporting sample size

Common study designs

review 172 observational cohort 101 cross-sectional survey 64 randomized controlled trial 54 theoretical or philosophical paper 48

Research

Synthesize the evidence → Search all →

Rational design, synthesis, and characterization of a solid Δ9-tetrahydrocannabinol (THC) nanoformulation suitable for “microdosing” applications

Abhinandan Banerjee, William Hosie, Ana Carolina Terso Ventura et al.

A THC-loaded nanoemulsion was created using an ethanol-assisted method without specialized equipment, producing lipid droplets averaging 190 nm. The nanoemulsion remained colloidally stable for at least six weeks, with no significant loss of cannabinoid potency. It withstood heat, freeze/thaw cycles, carbonation, dilution, high sucrose, and a pH range of 5-8. The nanoemulsion was converted into a water-soluble powder via lyophilization and ball-milling, suitable for microdosing applications. The powder was freely redispersible in water without phase separation, though it had limited free-flowing behavior.

DOI: 10.26434/chemrxiv-2023-zdt5s

Individual differences in the pharmacokinetic profiling of Δ9-THC may be associated with differential motivational effects of Δ9-THC on cognitive performance

Teneisha M. Myers, Noah C. Neverette, Aaron S. Devanathan et al. preprint

Acute restraint stress and THC did not impair working memory in rats. However, a 3 mg/kg dose of THC disrupted motivation-related task engagement in some rats, while others were unaffected. Those that stopped responding had higher plasma THC and metabolite concentrations than those that continued. Individual differences in THC metabolism may explain why some people experience adverse cognitive or motivational effects after cannabis use, while others do not.

DOI: 10.1101/2025.09.30.679373

Influence of solvent, sex, and age on pharmacokinetic and acute behavioral effects of vaporized cannabis extract in mice

S.R. Westbrook, A.L. Jensen, V. Copeland-Solorzano et al. preprint

Vaporized cannabis extract dissolved in polyethylene glycol 400 (PEG) produces higher plasma THC levels and stronger behavioral effects than when dissolved in propylene glycol/vegetable glycerol. In mice, the highest dose (300 mg/ml) caused reduced body temperature, pain sensitivity, and movement. Adolescent mice were less sensitive to the movement-suppressing effects than adults, and female mice metabolized THC more slowly than males, though no sex differences in acute behavioral effects were observed.

DOI: 10.1101/2025.01.10.632469

A Cross-Sectional Survey on Depersonalization/Derealization and Meditation-Induced Alterations of the Self

Erola Pons, Julieta Galante, Axel Lindner preprint

Meditation can trigger states phenomenologically similar to depersonalization/derealization (DPDR), but these experiences are typically rated as more positive, welcome, and spiritually meaningful than DPDR triggered by trauma, stress, or cannabis. In a cross-sectional survey comparing 60 people whose DPDR-like experiences came from meditation with 61 whose came from other triggers, the two groups scored similarly on the Cambridge Depersonalisation Scale but differed on measures of mysticism, ego dissolution, challenging experiences, and mindfulness. Most participants in both groups described their experiences as mixed, yet the meditation group rated them as much more positive. The findings suggest that contemplative approaches could inform clinical support for DPDR and that guidance is needed within meditation settings.

DOI: 10.31234/osf.io/6kyz9_v1

Cannabis induced psychosis: A comparative study between cannabis use disorder and cocaine use disorder

Maurizio Coppola, Raffaella Mondola preprint

Psychosis involves delusions and hallucinations without insight, arising from primary psychiatric illness or brain damage from substances, neurological diseases, or other medical conditions. Genetic, environmental, and gene-environment interactions contribute. Among environmental factors, psychotropic substances are key removable facilitators. This retrospective study compared substance-induced psychosis prevalence between outpatients with cannabis use disorder and those with cocaine use disorder, excluding those with personal or family psychiatric history.

DOI: 10.20944/preprints202310.0311.v1

Insular Cortical Thinning and Altered Structural Connectivity in Chronic Cannabis Users: A High-Resolution Morphometry and Diffusion Tractography Study

Fouad Meraji Far, Hamid Reza Banafshe, Amir Ghaderi et al.

Chronic cannabis use is associated with thinning of the insular cortex, a brain region involved in craving and self-awareness, and with altered white matter connections between the insula and other brain areas. In a sample of 13 male chronic cannabis users compared to 13 male non-users, MRI scans showed bilateral insular thinning without volume loss, reduced total gray matter volume, and lower volumes in the brainstem, left amygdala, right thalamus, left cerebellar cortex, and right orbitofrontal gyrus. Tractography revealed reduced diffusivity in left insula–amygdala pathways and lower fractional anisotropy in several insula–cortical connections. These findings suggest that circuits supporting salience, interoception, and emotional valuation are preferentially disrupted, which may contribute to compulsive cannabis use.

DOI: 10.21203/rs.3.rs-9801898/v1

Legalizing Magic Mushrooms: A Different Set of Laws for a Different Kind of Drug

Edward S. Adams

This article examines how the cannabis industry is regulated, tracing its origins, history, and flaws. It then compares the cannabis and psilocybin industries, arguing that the cannabis regulatory model should not be copied for psilocybin. Instead, the author proposes customized regulatory approaches that address psilocybin's distinct features, aiming to create a safe, effective, and well-regulated market.

DOI: 10.2139/ssrn.7094518

Unveiling the Sacred Plant: Reidentifying Soma, Haoma, and the Assyrian Sacred Tree

Milind Raskar

A multidisciplinary investigation combining textual analysis, fieldwork in India's Kutch region, and comparative ethnobotany identifies Vernonia cinerascens Sch. Bip. as a strong candidate for the sacred Soma plant of the Rigveda and its Iranian counterpart Haoma. The plant's woody stems, arrow-like shoots, tawny color, and leafy sprigs match ancient descriptions. Pressing its branches yielded a golden-tawny juice with a crackling sound noted in hymns. Experiential trials reported psychoactive and healing effects—relaxation, enhanced concentration, pain relief, calm joy—similar to those praised in the texts. The plant's known medicinal uses in African ethnobotany for mental disorders and depression further support the identification. Comparisons with Assyrian sacred tree iconography and Zoroastrian Barsom ritual suggest a broader Near Eastern continuity of sacred plant traditions.

DOI: 10.31235/osf.io/5sxaq_v1

The FDA Backdoor to MDMA Rescheduling

SSRN Electronic Journal Vincent Joralemon

The Drug Enforcement Administration (DEA) classifies MDMA as a Schedule I controlled substance, the most restrictive category under the Controlled Substances Act. However, Lykos Therapeutics (formerly MAPS PBC) has submitted a New Drug Application for MDMA-assisted therapy for PTSD. If the FDA approves this drug, it would provide the 'accepted medical use' that Schedule I drugs are statutorily denied, triggering a rescheduling process. Based on precedents like XYWAV and cannabis-derived medications, the DEA would likely reschedule only the specific FDA-approved drug product—likely to be marketed as RENSANSE—to Schedule II or III, while raw MDMA remains on Schedule I. This mechanism offers a model for incrementally relaxing federal restrictions on psychedelic substances and expanding research access.

DOI: 10.2139/ssrn.6960838

Functional recovery trajectories in cannabis-induced first-episode psychosis: The role of dissociative symptoms in the discrepancy between symptomatic improvement and functional outcomes.

Psychiatry research September 1, 2026 Valerio Ricci, Andrea Paggi, Giovanni Martinotti et al.

In patients with cannabis-induced first-episode psychosis, dissociative symptoms—especially depersonalization and derealization—are strong independent predictors of poor functional recovery over 24 months. Among 72 patients, three recovery trajectories emerged: Rapid Recovery (34.7%, GAF +29.1 points), Gradual Recovery (40.3%, GAF +15.7 points), and Persistent Impairment (25.0%, GAF +4.7 points). A symptom-function discrepancy occurred in 31.9% of patients, where psychotic symptoms improved but functioning did not; these patients had higher baseline dissociation scores (33.8 vs. 18.1). Dissociation mediated 35% of cannabis's negative effect on functional outcomes. A high-risk subgroup (22%) with elevated dissociation, depression, and continued cannabis use showed minimal improvement despite treatment. Routine dissociation assessment and targeted interventions may improve outcomes.

DOI: 10.1016/j.psychres.2026.117240 Full text Cannabis-induced psychosis Depersonalization Dissociation First-episode psychosis +1

Clinical trials

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