The Construct of Medical and Non-Medical Marijuana—Critical Review
2. Literature Review
4.1. The Neurobiology of Cannabis-Induced Psychoses
4.2. Do Cannabinoids Cause or Heal Psychoses?
4.3. Cannabis and Its Anxiolytic Properties
4.4. Cannabis and Post-Traumatic Stress Disorder
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
|AIS||Analogue Intoxication Scale|
|ANOVA||Analysis of Variance|
|BMI||Body Mass Index|
|BSPS||Brief Social Phobia Scale|
|BSS||Bodily Symptoms Scale|
|CAPS||Clinician-Administered Posttraumatic Scale|
|CB1R||Cannabinoid type 1 receptor|
|CGI||Clinical Global Impression|
|CGI-C||Clinical Global Impression of Change|
|CGI-I||Clinical Global Impression of Improvement|
|CGI-S||Clinical Global Impression of Severity|
|COWAT||Controlled Oral Word Association Test|
|DSM-IV||Diagnostic and Statistical Manual of Mental Disorders|
|DSST||Digit-Symbol Substitution Test|
|DTI||Diffusion Tensor Imaging|
|GAF||Global Assessment of Functioning|
|LSD||Lysergic Acid Diethylamide|
|MINI-SPIN||Mini Social Phobia Inventory|
|MRI||Magnetic Resonance Imaging|
|NES||Nightmare Effects Survey|
|NFQ||Nightmare Frequency Questionnaire|
|PTSD||Post-Traumatic Stress Disorder|
|REM||Rapid Eye Movement|
|SAD||Social Anxiety Disorder|
|SCID-CV||Structured Clinical Interview for DSM-IV, Clinical Version|
|SCR||Skin Conductance Response|
|SIPD||Substance-induced psychotic disorder|
|SPECT||Single-Photon Emission Computerized Tomography|
|SPIN||Social Phobia Inventory|
|SPM8||Statistical Parametric Mapping|
|SPS||Simulated Public Speaking|
|SPSS-N||Negative Self-Statements Public Speaking Scale|
|SPST||Simulation Public Speaking Test|
|STAI||Spielberger State-Trait Anxiety Inventory|
|STU||Secure Treatment Unit|
|TRPV1||Transient Receptor Potential Vanilloid type 1 channel|
|VAMS||Visual Analog Mood Scale|
|WBQ||General Well Being Questionnaire|
|WMS-III||Wechsler Memory Scale (3rd edition)|
|5-HT1a||5-hydroxytryptamine (serotonin) 1A receptor|
|18-FDG-PET||18-Fluoro-2-deoxyglucose Positron Emission Tomography|
|Authors and Date||Study Type and Research Design||Sample Characteristics||Cannabis Exposure||Experimental and Control Intervention||Outcomes|
|Zuardi AW, Shirakawa I, Finkelfarb E, and Karniol IG. (1982)||Quantitative|
Double-blind randomized controlled trial
|n = 8|
Male (n = 6)
Female (n = 2)
Aged 20–30 years ( = 27)
|Marijuana use (n = 5) no less than 15 days prior to the experiment||A mixture of 0.5 mg/kg Δ9-THC and 1 mg/kg CBD|
A mixture of 0.5 mg/kg Δ9-THC and I mg/kg CBD
Diazepam, 10 mg
|Δ9-THC’s anxiogenic properties led to a substantial elevation of anxiety, which was partially antagonized by CBD|
Subjective alterations provoked by Δ9-THC diminished with simultaneous CBD administration
CBD’s effects seem to be connected to the antagonism of effects between the two cannabinoids
|A.W. Zuardi, R.A. Cosme, F.G. Graeff, and F.S. Guimarães (1993)||Quantitative|
Double-blind randomized controlled trial
|n = 40|
Male (n = 18)
Female (n = 22)
Aged 20–30 years ( = 22.8)
Paid volunteers, recruited from university students of Medicine and psychology courses
|Not specified||Identical gelatin capsules with:|
CBD, 300 mg
Diazepam, 10 mg
Ipsapirone, 5 mg
|Ipsapirone attenuated SPS-induced anxiety (and systolic blood pressure), while CBD reduced anxiety experienced after the SPS test|
Diazepam held significant sedative and anxiolytic effects and had no effect on the increase of SPS test-induced anxiety
The SPS test is sensitive to drug effects and induces reliable increases in anxiety
|Fusar-Poli P, Crippa JA, and Bhattacharyya S, et al. (2009)||Quantitative|
Double-blind, randomized, and placebo-controlled design
|n = 15|
Aged 18–35 ( = 26.67, SD = 5.7)
Recruitment strategy not specified.
|No cannabis use in the last month. Lifetime exposure of <15 times.||Gelatin capsules containing:|
Δ9-THC, 10 mg
CBD, 600 mg
|Cannabidiol reduced the neurofunctional engagement of the amygdala and the cingulate cortex at fearful stimuli exposure, which was correlated with a decrease in the electrodermal response, consistent with its reported anxiolytic effects|
Δ9-THC was associated with an increase in anxiety and electrodermal response. It also modulated activation in parietal and frontal areas
|Fraser GA. (2009)||Quantitative|
Open-label clinical trial design
|n = 47|
Male (n = 20)
Female (n = 27)
( = 44, SD = 9)
Patients referred to a psychiatric specialist outpatient clinic by other physicians
|Screened for previous negative experiences with marijuana use||Average effective dose of Nabilone = 0.5 mg (range: 0.2–4.0 mg)|
|The majority of patients experienced either a cessation or significant reduction in nightmare intensity|
Some reported an improvement in sleep quality and time, and a reduction in night sweats and daytime flashbacks
Nabilone proved to be beneficial in patients with treatment-naïve nightmares, within the course of PTSD
|Jetly R, Heber A, Fraser G, and Boisvert D. (2014)||Quantitative|
Preliminary randomized, double-blind
placebo-controlled cross-over design
|n = 10|
Aged 18–65 ( = 43.6, SD = 8.2)
Patients referred to a military treatment clinic
Nabilone, 0.5 mg
Titrated to an effective, maximum dose of:
Nabilone, 3.0 mg
|Nabilone produced large or significant improvements in 70% of the patients|
Nabilone significantly reduced the frequency and intensity of nightmares
Nabilone was well-tolerated by the patients
|Roitman P, Mechoulam R, Cooper-Kazaz R, and Shalev A. (2014)||Quantitative|
Preliminary, open-label pilot study design
|n = 10|
Male (n = 7),
Female (n = 3)
Age ( = 52.3, SD = 8.3)
Recruited from mental health clinics in Jerusalem, Israel
|No cannabis use at least 6 months before the study||Starting dose:|
THC, 2.5 mg twice/day
Final dose (if increased):
THC, 5.0 mg twice/day
|Significant improvements in sleep quality, nightmare frequency, and PTSD hyperarousal symptoms|
20% of patients attained total nightmare remission
Orally absorbable Δ (9)-THC was safe and well tolerated by patients with chronic PTSD
|Crippa JA, Derenusson GN, Ferrari TB, et al. (2010)||Quantitative|
Double-blind placebo-controlled design
|n = 10|
Aged 20–33 years ( = 24.2, SD = 3.7)
Recruited from an epidemiological sample of 2320 university students, selected via a screening procedure
|Lifetime exposure of <5 times|
No marijuana use in the year prior to the study
No illegal drug use
|Gelatin capsules containing:|
CBD, 400 mg
|Acute CBD administration has the potential to reduce subjective anxiety in SAD patients, possibly due to CBD’s altering effect on the functional activity of brain areas involved in anxiety processing|
CBD, relative to placebo, led to significant decrements in the parahippocampal activity
The anxiolytic effects of CBD were not attributable to sedation
|Bergamaschi MM, Queiroz RH, Chagas MH, et al. (2011)||Quantitative|
Double-blind randomized placebo-controlled trial
|n = 36|
SAD patients (n = 24)
Healthy control group (n = 12)
Recruited from 2319 undergraduate students, screened for probable SAD
Groups matched according to sex, age, years of education, and socioeconomic status
|Lifetime exposure of <5 times|
No marijuana use in the year prior to the study
No illegal drug use
|CBD gelatin capsules, 600 mg|
Placebo gelatin capsules
|CBD inhibits one of the main symptoms of SAD-speaking in public|
CBD pretreatment significantly reduced the anxiety, cognitive impairment, and discomfort in SAD patients’ speech performance and alert in their anticipatory speech
An increase in negative self-evaluations presented by the placebo group (significantly greater cognitive impairment, higher anxiety, alert, and discomfort) was almost abolished in the CBD group
|Authors and Date||Aim||Eligibility: Inclusion and Exclusion Criteria||Analysis and Data Extraction||Results||Conclusions|
|Khoury et al. (2017)||The aim was to assess the use of CBD in the treatment of anxiety disorders, schizophrenia, psychotic disorders, bipolar disorder, depression, and substance use disorders.|
Emphasis was put on exploring the benefits and adverse events of cannabidiol’s applications in the aforementioned psychiatric conditions.
|Assessment of CBD’s therapeutic use in the treatment of anxiety, psychosis, schizophrenia, depressive disorder, or substance use disorders.|
All types of study designs were included.
Pre-clinical studies, expert opinions, literature reviews, research not pertaining to psychiatric disorders of interest, and duplicates were excluded from the analysis.
|World Federation of Societies of Biological Psychiatry (WFSBP) guidelines were followed throughout the classification process. |
The Specific data sections, including references, study design, participant characteristics, primary goals, sample size, intervention type, results, and main limitations were extracted from the studies whenever possible.
|Identification of 596 papers and 104 registered clinical trials that included CBD as a treatment strategy.|
34 records included in the final analysis:
Registered clinical trials: (n = 21)
Articles: (n = 13)
|Evidence on the use of CBD in acute anxiety and long-term SAD treatment was derived from uncontrolled studied, which lacked support.|
No identified studies assessing the impact of CBD on other anxiety disorders.
Evidence for the short-term treatment of treatment resistant schizophrenia (TRS) arose from uncontrolled studies and lacked evidence.
Negative evidence was found for first episode of schizophrenia.
Evidence on the use of CBD in Cannabis dependence came from case reports and lacked evidence.
Scarce evidence exists on the safety as well as the efficacy of CBD in the field of psychiatry.
Well-designed, substantially larger RCT’s are crucial in order to assess the effects of CBD in psychiatric disorders.
|Betthauser K, Pilz J, Vollmer LE. (2015)||The objective was to review the existing data on the efficacy, safety, and tolerability of cannabinoids in military veterans with PTSD.||Cannabinoids’ general use in persons with a PTSD diagnosis or cannabinoids’ use in the amelioration of PTSD symptoms, both in relation to military experience.|
Research in humans.
Subjects with diagnosed PTSD via a standard scale (ex. DSM-IV, or DSM-V).
Editorials and opinion pieces were excluded.
|Each item was analyzed both individually and collaboratively by the authors so as to establish its clinical relevance.||59 articles were identified via the database search.|
11 articles were included in the final review.
A variety of study designs were included in the final selection.
|Further research in regards to cannabinoid’s therapeutic effects on PTSD symptoms is needed. The identified evidence mainly lacked randomization, a representative and sizeable sample, and placebo control.|
The assessed evidence suggests that some military veterans with PTSD use cannabis or its derivatives in order to control their PTSD symptoms. Some patients report benefits, such as reduced anxiety, insomnia, and improved coping ability. Further inquiry is much needed in order to get a better understanding of the phenomenon.
In general, the articles supported two concepts:
1. Cannabis is used by persons with PTSD for symptom alleviation.
2. Some find cannabis to be beneficial in that sense.
|Lim K, See YM, Lee J. (2017)||The aim was to provide a more extensive evaluation of the efficacy regarding medical uses of cannabinoids, specifically with regard to psychiatric, movement, and neurogenerative disorders.||RCT’s that compared and examined cannabis (as a pharmacological intervention) with placebo, usual care, cannabis derivatives, or other active treatments.|
Human studies on subjects of any sex and age, clinically diagnosed with: movement disorders, neurological conditions and psychiatric conditions.
Quantitative studies, as well as opinion and discussion papers, were excluded.
|Data on the study type, sample profile, intervention dosage and type, primary outcome measures, and side effects and adverse events were extracted from each report.|
Methodological validity was assessed by two independent raters with the use of the Cochrane risk of bias tool. Any discrepancies were resolved through a discussion.
|931 hits were originally identified.|
24 records were included in the final review:
Crossover trials (n = 18)
Parallel trials (n = 6)
The final study selection consisted of studies conducted in Western societies.
|Although some trials reported positive findings in relation to anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer’s disease and dementia, Huntington’s disease, and Tourette syndrome, and dyskinesia in Parkinson’s disease, a certain conclusion cannot be drawn from them.|
The evaluation of the trials’ resulted in an unclear risk of bias. It also indicated methodological issues such as inadequate descriptions of allocation concealment, blinding, and small sample sizes.
More methodologically valid controlled trials are needed in order to assess both the long-term and short-term efficacy, tolerability, and safety of cannabis use in medicine along with the mechanisms underlying its therapeutic potential.
|Whiting PF, Wolff RF, Deshpande S, et al. (2015)||The objective was to systematically review the benefits and adverse effects of cannabinoids’ use in the field of medicine.||RCT’s comparing cannabinoids with placebo, usual care or no treatment in nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis (MS) or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, intra- ocular pressure in glaucoma, or Tourette syndrome.|
No language restriction.
Nonrandomized studies, including uncontrolled studies, in which more than 25 patients were eligible.
|The data extraction was done by two independent reviewers and involved: categorical and continuous data, baseline characteristics and outcomes, reported between-group statistical analyses, and full contents.|
The study quality was assessed with the Cochrane risk of bias tool.
Data were pooled using random-effects-meta-analysis if possible.
Dichotomous data: odds ratio (OR) and confidence interval (CI) measures.
The focus was on peer-reviewed articles.
|23,754 hits were originally identified.|
A total of 79 studies, available as 151 reports, were included in the final review:
Parallel trials: (n = 34)
Cross-over trials: (n = 45)
Publication date range: 1975–2015 (ME = 2004).
5%: low risk of bias
70%: high risk of bias
25% unclear risk of bias
|In terms of anxiety disorders, only one small parallel-group trial was judged to be at high risk of bias was identified. Other reports pertaining to anxiety in patients with chronic pain reported a larger benefit to cannabinoid use rather than placebo, but the studies were not restricted to anxiety disorder patients.|
Two studies were identified in relation to psychosis and judged at high risk of bias. No differences in mental health outcomes were found between treatment groups.
In terms of improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette’s syndrome, only low-quality evidence was found.
An association was found between Cannabinoids and increased risk of short-term adverse effects (including serious adverse effects). The most commonly occurring adverse effects included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucinations.
- Han, B.; Compton, W.M.; Blanco, C.; Jones, C.M. Trends in and correlates of medical marijuana use among adults in the United States. Drug Alcohol Depend. 2018, 186, 120–129. [Google Scholar] [CrossRef] [PubMed]
- Murray, R.; Englund, A.; Abi-Dargham, A.; Lewis, D.; Di Forti, M.; Davies, C.; Sherif, M.; McGuire, P.; D’Souza, D. Cannabis-associated psychosis: Neural substrate and clinical impact. Neuropharmacology 2017, 124, 89–104. [Google Scholar] [CrossRef] [PubMed]
- Englund, A.; Freeman, T.; Murray, R.; McGuire, P. Can we make cannabis safer? Lancet Psychiatry 2017, 4, 643–648. [Google Scholar] [CrossRef][Green Version]
- Colizzi, M.; Murray, R. Cannabis and psychosis: What do we know and what should we do? Br. J. Psychiatry 2018, 212, 195–196. [Google Scholar] [CrossRef]
- Marconi, A.; Di Forti, M.; Lewis, C.; Murray, R.; Vassos, E. Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. Schizophr. Bull. 2016, 42, 1262–1269. [Google Scholar] [CrossRef]
- Böcker, K.B.E.; Hunault, C.C.; Gerritsen, J.; Kruidenier, M.; Mensinga, T.T.; Kenemans, J.L. Cannabinoid Modulations of Resting State EEG Theta Power and Working Memory Are Correlated in Humans. J. Cogn. Neurosci. 2010, 22, 1906–1916. [Google Scholar] [CrossRef] [PubMed]
- Sutcliffe, G.; Harneit, A.; Tost, H.; Meyer-Lindenberg, A. Neuroimaging Intermediate Phenotypes of Executive Control Dysfunction in Schizophrenia. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2016, 1, 218–229. [Google Scholar] [CrossRef]
- Freeman, D.; Dunn, G.; Murray, R.M.; Evans, N.; Lister, R.; Antley, A.; Slater, M.; Godlewska, B.; Cornish, R.; Williams, J.; et al. How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆ 9 -Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia. Schizophr. Bull. 2014, 41, 391–399. [Google Scholar] [CrossRef][Green Version]
- Gorka, A.X.; Knodt, A.R.; Hariri, A.R. Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity. Soc. Cogn. Affect. Neurosci. 2014, 10, 501–507. [Google Scholar] [CrossRef][Green Version]
- Back, F.P.; Carobrez, A.P. Periaqueductal gray glutamatergic, cannabinoid and vanilloid receptor interplay in defensive behavior and aversive memory formation. Neuropharmacology 2018, 135, 399–411. [Google Scholar] [CrossRef]
- Rocchetti, M.; Crescini, A.; Borgwardt, S.; Caverzasi, E.; Politi, P.; Atakan, Z.; Fusar-Poli, P. Is cannabis neurotoxic for the healthy brain? A meta-analytical review of structural brain alterations in non-psychotic users. Psychiatry Clin. Neurosci. 2013, 67, 483–492. [Google Scholar] [CrossRef] [PubMed]
- Koenders, L.; Lorenzetti, V.; De Haan, L.; Suo, C.; Vingerhoets, W.; Brink, W.V.D.; Wiers, R.; Meijer, C.J.; Machielsen, M.; Goudriaan, A.E.; et al. Longitudinal study of hippocampal volumes in heavy cannabis users. J. Psychopharmacol. 2017, 31, 1027–1034. [Google Scholar] [CrossRef] [PubMed]
- Lorenzetti, V.; Solowij, N.; Whittle, S.; Fornito, A.; Lubman, D.I.; Pantelis, C.; Yucel, M. Gross morphological brain changes with chronic, heavy cannabis use. Br. J. Psychiatry 2015, 206, 77–78. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Cheng, D.; Spiro, A.S.; Jenner, A.M.; Garner, B.; Karl, T. Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer’s Disease Transgenic Mice. J. Alzheimer’s Dis. 2014, 42, 1383–1396. [Google Scholar] [CrossRef]
- Filbey, F.M.; Dunlop, J. Differential reward network functional connectivity in cannabis dependent and non-dependent users. Drug Alcohol Depend. 2014, 140, 101–111. [Google Scholar] [CrossRef][Green Version]
- Lopez-Larson, M.P.; Rogowska, J.; Yurgelun-Todd, D. Aberrant orbitofrontal connectivity in marijuana smoking adolescents. Dev. Cogn. Neurosci. 2015, 16, 54–62. [Google Scholar] [CrossRef][Green Version]
- Orr, J.M.; Paschall, C.J.; Banich, M. Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry. NeuroImage Clin. 2016, 12, 47–56. [Google Scholar] [CrossRef][Green Version]
- D’Souza, D.C.; Cortes-Briones, J.A.; Ranganathan, M.; Thurnauer, H.; Creatura, G.; Surti, T.; Planeta, B.; Neumeister, A.; Pittman, B.; Normandin, M.; et al. Rapid Changes in Cannabinoid 1 Receptor Availability in Cannabis-Dependent Male Subjects After Abstinence from Cannabis. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2016, 1, 60–67. [Google Scholar] [CrossRef][Green Version]
- Bloomfield, M.A.; Ashok, A.H.; Volkow, N.D.; Howes, O.D. The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature 2016, 539, 369–377. [Google Scholar] [CrossRef]
- Howes, O.; Kapur, S. A neurobiological hypothesis for the classification of schizophrenia: Type a (hyperdopaminergic) and type B (normodopaminergic). Br. J. Psychiatry 2014, 205, 1–3. [Google Scholar] [CrossRef]
- Radhakrishnan, R.; Skosnik, P.D.; Cortes-Briones, J.; Sewell, R.A.; Carbuto, M.; Schnakenberg, A.; Cahill, J.; Bois, F.; Gunduz-Bruce, H.; Pittman, B.; et al. GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC. Neuropsychopharmacology 2015, 40, 2047–2056. [Google Scholar] [CrossRef][Green Version]
- Prescot, A.P.; Renshaw, P.F.; Yurgelun-Todd, D.A. γ-Amino butyric acid and glutamate abnormalities in adolescent chronic marijuana smokers. Drug Alcohol Depend. 2013, 129, 232–239. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Wiesbeck, G.A.; Taeschner, K.-L. A cerebral computed tomography study of patients with drug-induced psychoses. Eur. Arch. Psychiatry Clin. Neurosci. 1991, 241, 88–90. [Google Scholar] [CrossRef] [PubMed]
- Cunha, P.J.; Rosa, P.G.P.; Ayres, A.D.M.; Duran, F.L.; Santos, L.C.; Scazufca, M.; Menezes, P.R.; dos Santos, B.; Murray, R.M.; Crippa, J.A.S.; et al. Cannabis use, cognition and brain structure in first-episode psychosis. Schizophr. Res. 2013, 147, 209–215. [Google Scholar] [CrossRef] [PubMed]
- Dragogna, F.; Mauri, M.C.; Marotta, G.; Armao, F.T.; Brambilla, P.; Altamura, A.C. Brain Metabolism in Substance-Induced Psychosis and Schizophrenia: A Preliminary PET Study. Neuropsychobiology 2014, 70, 195–202. [Google Scholar] [CrossRef]
- James, A.; Hough, M.; James, S.; Winmill, L.; Burge, L.; Nijhawan, S.; Matthews, P.; Zarei, M. Greater white and grey matter changes associated with early cannabis use in adolescent-onset schizophrenia (AOS). Schizophr. Res. 2011, 128, 91–97. [Google Scholar] [CrossRef]
- Andréasson, S.; Engström, A.; Allebeck, P.; Rydberg, U. Cannabis and Schizophrenia a Longitudinal Study of Swedish Conscripts. Lancet 1987, 330, 1483–1486. [Google Scholar] [CrossRef]
- Dragt, S.; Nieman, D.H.; E Becker, H.; van de Fliert, R.; Dingemans, P.M.; de Haan, L.; van Amelsvoort, T.A.; Linszen, D.H. Age of Onset of Cannabis Use is Associated with Age of Onset of High-Risk Symptoms for Psychosis. Can. J. Psychiatry 2010, 55, 165–171. [Google Scholar] [CrossRef][Green Version]
- Bagot, K.S.; Milin, R.; Kaminer, Y. Adolescent Initiation of Cannabis Use and Early-Onset Psychosis. Subst. Abus. 2015, 36, 524–533. [Google Scholar] [CrossRef]
- Moore, T.H.; Zammit, S.; Lingford-Hughes, A.; Barnes, T.R.; Jones, P.B.; Burke, M.; Lewis, G. Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review. Lancet 2007, 370, 319–328. [Google Scholar] [CrossRef][Green Version]
- Bhattacharyya, S.; Morrison, P.D.; Fusar-Poli, P.; Martin-Santos, R.; Borgwardt, S.; Wintonbrown, T.T.; Nosarti, C.; Carroll, C.M.O.; Seal, M.L.; Allen, P.; et al. Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology. Neuropsychopharmacology 2009, 35, 764–774. [Google Scholar] [CrossRef] [PubMed]
- Broyd, S.J.; Van Hell, H.H.; Beale, C.; Yücel, M.; Solowij, N. Acute and Chronic Effects of Cannabinoids on Human Cognition—A Systematic Review. Biol. Psychiatry 2016, 79, 557–567. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Curran, H.V.; Freeman, T.; Mokrysz, C.; Lewis, D.; Morgan, C.J.A.; Parsons, L.H. Keep off the grass? Cannabis, cognition and addiction. Nat. Rev. Neurosci. 2016, 17, 293–306. [Google Scholar] [CrossRef] [PubMed]
- D’Souza, D.C.; Perry, E.; MacDougall, L.; Ammerman, Y.; Cooper, T.; Wu, Y.-T.; Braley, G.; Gueorguieva, R.; Krystal, J.H. The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis. Neuropsychopharmacology 2004, 29, 1558–1572. [Google Scholar] [CrossRef]
- Moreau, J.J. Hashish and Mental Illness; Peters, H., Nahas, G.G., Eds.; Raven Press: New York, NY, USA, 1973. [Google Scholar]
- Morrison, P.D.; Stone, J.M. Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation. Hum. Psychopharmacol. Clin. Exp. 2011, 26, 77–80. [Google Scholar] [CrossRef]
- Morrison, P.D.; Zois, V.; McKeown, D.A.; Lee, T.D.; Holt, D.W.; Powell, J.; Kapur, S.; Murray, R. The acute effects of synthetic intravenous Δ9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol. Med. 2009, 39, 1607–1616. [Google Scholar] [CrossRef]
- Freeman, D.; Morrison, P.D.; Murray, R.M.; Evans, N.; Lister, R.; Dunn, G. Persecutory ideation and a history of cannabis use. Schizophr. Res. 2013, 148, 122–125. [Google Scholar] [CrossRef]
- Hollis, C.; Groom, M.J.; Das, D.; Calton, T.; Bates, A.T.; Andrews, H.K.; Jackson, G.M.; Liddle, P.F. Different psychological effects of cannabis use in adolescents at genetic high risk for schizophrenia and with attention deficit/hyperactivity disorder (ADHD). Schizophr. Res. 2008, 105, 216–223. [Google Scholar] [CrossRef]
- Altintas, M.; Inanc, L.; Oruc, G.A.; Arpacioglu, S.; Gulec, H. Clinical characteristics of synthetic cannabinoid-induced psychosis in relation to schizophrenia: A single-center cross-sectional analysis of concurrently hospitalized patients. Neuropsychiatr. Dis. Treat. 2016, 12, 1893–1900. [Google Scholar] [CrossRef][Green Version]
- Patel, S.J.; Khan, S.; M, S.; Hamid, P. The Association Between Cannabis Use and Schizophrenia: Causative or Curative? A Systematic Review. Cureus 2020, 12, e9309. [Google Scholar] [CrossRef]
- Atakan, Z.; Bhattacharyya, S.; Allen, P.; Martinsantos, R.; Crippa, J.A.; Borgwardt, S.; Fusar-Poli, P.; Seal, M.; Sallis, H.; Stahl, D.; et al. Cannabis affects people differently: Inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: A functional magnetic resonance imaging study with healthy volunteers. Psychol. Med. 2012, 43, 1255–1267. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Iseger, T.A.; Bossong, M.G. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr. Res. 2015, 162, 153–161. [Google Scholar] [CrossRef] [PubMed]
- Englund, A.; Morrison, P.D.; Nottage, J.F.; Hague, D.; Kane, F.; Bonaccorso, S.; Stone, J.M.; Reichenberg, A.; Brenneisen, R.; Holt, D.; et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J. Psychopharmacol. 2012, 27, 19–27. [Google Scholar] [CrossRef]
- Zuardi, A.W.; Morais, S.L.; Guimarães, F.S.; Mechoulam, R. Antipsychotic effect of cannabidiol. J. Clin. Psychiatry 1995, 56, 485–486. [Google Scholar]
- Leweke, F.M.; Piomelli, D.; Pahlisch, F.; Muhl, D.; Gerth, C.W.; Hoyer, C.; Klosterkötter, J.; Hellmich, M.; Koethe, D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry 2012, 2, e94. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Leweke, F.M.; Mueller, J.K.; Lange, B.; Rohleder, C. Therapeutic Potential of Cannabinoids in Psychosis. Biol. Psychiatry 2016, 79, 604–612. [Google Scholar] [CrossRef] [PubMed]
- Kane, J.; Honigfeld, G.; Singer, J.; Meltzer, H. Clozapine for the Treatment-Resistant Schizophrenic. Arch. Gen. Psychiatry 1988, 45, 789–796. [Google Scholar] [CrossRef]
- Khoury, J.M.; Neves, M.D.C.L.D.; Roque, M.A.V.; Queiroz, D.A.D.B.; De Freitas, A.A.C.; De Fátima, Â.; Moreira, F.A.; Garcia, F.D. Is there a role for cannabidiol in psychiatry? World J. Biol. Psychiatry 2017, 20, 101–116. [Google Scholar] [CrossRef]
- Zuardi, A.W.; Shirakawa, I.; Finkelfarb, E.; Karniol, I.G. Action of cannabidiol on the anxiety and other effects produced by ?9-THC in normal subjects. Psychopharmacology 1982, 76, 245–250. [Google Scholar] [CrossRef]
- Zuardi, A.W.; Cosme, R.A.; Graeff, F.; Guimarães, F.S. Effects of ipsapirone and cannabidiol on human experimental anxiety. J. Psychopharmacol. 1993, 7, 82–88. [Google Scholar] [CrossRef]
- Fusar-Poli, P.; Crippa, J.A.; Bhattacharyya, S.; Borgwardt, S.J.; Allen, P.; Martin-Santos, R.; Seal, M.; Surguladze, S.A.; O’Carrol, C.; Atakan, Z.; et al. Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing. Arch. Gen. Psychiatry 2009, 66, 95–105. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Crippa, J.A.S.; Derenusson, G.N.; Ferrari, T.B.; Wichert-Ana, L.; Duran, F.L.; Martin-Santos, R.; Simões, M.V.; Bhattacharyya, S.; Fusar-Poli, P.; Atakan, Z.; et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. J. Psychopharmacol. 2010, 25, 121–130. [Google Scholar] [CrossRef] [PubMed]
- Bergamaschi, M.M.; Queiroz, R.H.C.; Chagas, M.H.N.; De Oliveira, D.C.G.; De Martinis, B.; Kapczinski, F.; de Quevedo, J.L.; Roesler, R.; Schroder, N.; Nardi, A.E.; et al. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacology 2011, 36, 1219–1226. [Google Scholar] [CrossRef] [PubMed]
- Fraguas-Sánchez, A.I.; Torres-Suárez, A.I. Medical Use of Cannabinoids. Drugs 2018, 78, 1665–1703. [Google Scholar] [CrossRef] [PubMed]
- Turna, J.; Patterson, B.; Van Ameringen, M. Is cannabis treatment for anxiety, mood, and related disorders ready for prime time? Depress. Anxiety 2017, 34, 1006–1017. [Google Scholar] [CrossRef]
- Noel, C. Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders. Ment. Health Clin. 2017, 7, 29–38. [Google Scholar] [CrossRef]
- Hill, M.N.; Campolongo, P.; Yehuda, R.; Patel, S. Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder. Neuropsychopharmacology 2018, 43, 80–102. [Google Scholar] [CrossRef][Green Version]
- Bonn-Miller, M.O.; Vujanovic, A.A.; Feldner, M.T.; Bernstein, A.; Zvolensky, M.J. Posttraumatic stress symptom severity predicts marijuana use coping motives among traumatic event-exposed marijuana users. J. Trauma. Stress 2007, 20, 577–586. [Google Scholar] [CrossRef]
- Rong, C.; Lee, Y.; Carmona, N.E.; Cha, D.S.; Ragguett, R.-M.; Rosenblat, J.D.; Mansur, R.B.; Ho, R.C.; McIntyre, R.S. Cannabidiol in medical marijuana: Research vistas and potential opportunities. Pharmacol. Res. 2017, 121, 213–218. [Google Scholar] [CrossRef]
- Lim, K.; See, Y.M.; Lee, J. A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders. Clin. Psychopharmacol. Neurosci. 2017, 15, 301–312. [Google Scholar] [CrossRef][Green Version]
- Jetly, R.; Heber, A.; Fraser, G.; Boisvert, D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology 2015, 51, 585–588. [Google Scholar] [CrossRef] [PubMed]
- Betthauser, K.; Pilz, J.; Vollmer, L.E. Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. Am. J. Health Pharm. 2015, 72, 1279–1284. [Google Scholar] [CrossRef] [PubMed]
- Fraser, G.A. The Use of a Synthetic Cannabinoid in the Management of Treatment-Resistant Nightmares in Posttraumatic Stress Disorder (PTSD). CNS Neurosci. Ther. 2009, 15, 84–88. [Google Scholar] [CrossRef] [PubMed]
- Greer, G.R.; Grob, C.S.; Halberstadt, A.L. PTSD Symptom Reports of Patients Evaluated for the New Mexico Medical Cannabis Program. J. Psychoact. Drugs 2014, 46, 73–77. [Google Scholar] [CrossRef]
- Roitman, P.; Mechoulam, R.; Cooper-Kazaz, R.; Shalev, A. Preliminary, Open-Label, Pilot Study of Add-On Oral Δ9-Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder. Clin. Drug Investig. 2014, 34, 587–591. [Google Scholar] [CrossRef]
- Cameron, C.; Watson, D.; Robinson, J. Use of a Synthetic Cannabinoid in a Correctional Population for Posttraumatic Stress Disorder–Related Insomnia and Nightmares, Chronic Pain, Harm Reduction, and Other Indications. J. Clin. Psychopharmacol. 2014, 34, 559–564. [Google Scholar] [CrossRef][Green Version]
- Steenkamp, M.M.; Blessing, E.M.; Galatzer-Levy, I.R.; Hollahan, L.C.; Anderson, W.T. Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review. Depress. Anxiety 2017, 34, 207–216. [Google Scholar] [CrossRef]
- Zer-Aviv, T.M.; Segev, A.; Akirav, I. Cannabinoids and post-traumatic stress disorder: Clinical and preclinical evidence for treatment and prevention. Behav. Pharmacol. 2016, 27, 561–569. [Google Scholar] [CrossRef]
- Whiting, P.; Wolff, R.F.; Deshpande, S.; Di Nisio, M.; Duffy, S.; Hernandez, A.V.; Keurentjes, J.C.; Lang, S.; Misso, K.; Ryder, S.; et al. Cannabinoids for Medical Use. JAMA J. Am. Med. Assoc. 2015, 313, 2456–2473. [Google Scholar] [CrossRef]
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Silczuk, A.; Smułek, D.; Kołodziej, M.; Gujska, J. The Construct of Medical and Non-Medical Marijuana—Critical Review. Int. J. Environ. Res. Public Health 2022, 19, 2769. https://doi.org/10.3390/ijerph19052769
Silczuk A, Smułek D, Kołodziej M, Gujska J. The Construct of Medical and Non-Medical Marijuana—Critical Review. International Journal of Environmental Research and Public Health. 2022; 19(5):2769. https://doi.org/10.3390/ijerph19052769Chicago/Turabian Style
Silczuk, Andrzej, Daria Smułek, Marcin Kołodziej, and Julia Gujska. 2022. "The Construct of Medical and Non-Medical Marijuana—Critical Review" International Journal of Environmental Research and Public Health 19, no. 5: 2769. https://doi.org/10.3390/ijerph19052769