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      The psychedelic effects of cannabis: A review of the literature

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          Abstract

          Cannabis and classic psychedelics are controlled substances with emerging evidence of efficacy in the treatment of a variety of psychiatric illnesses. Cannabis has largely not been regarded as having psychedelic effects in contemporary literature, despite many examples of historical use along with classic psychedelics to attain altered states of consciousness. Research into the “psychedelic” effects of cannabis, and delta-9-tetrahydrocannabinol (THC) in particular, could prove helpful for assessing potential therapeutic indications and elucidating the mechanism of action of both cannabis and classic psychedelics. This review aggregates and evaluates the literature assessing the capacity of cannabis to yield the perceptual changes, aversiveness, and mystical experiences more typically associated with classic psychedelics such as psilocybin. This review also provides a brief contrast of neuroimaging findings associated with the acute effects of cannabis and psychedelics. The available evidence suggests that high-THC cannabis may be able to elicit psychedelic effects, but that these effects may not have been observed in recent controlled research studies due to the doses, set, and settings commonly used. Research is needed to investigate the effects of high doses of THC in the context utilized in therapeutic studies of psychedelics aimed to occasion psychedelic and/or therapeutic experiences. If cannabis can reliably generate psychedelic experiences under these conditions, high-THC dose cannabis treatments should be explored as potential adjunctive treatments for psychiatric disorders and be considered as an active comparator in clinical trials involving traditional psychedelic medications.

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          Most cited references79

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          Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

          Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595
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            Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

            Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
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              Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

              Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. Trial Registration: ClinicalTrials.gov Identifier: NCT00957359
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Journal of Psychopharmacology
                J Psychopharmacol
                SAGE Publications
                0269-8811
                1461-7285
                November 10 2023
                Affiliations
                [1 ]Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
                [2 ]Department of Psychiatry and Behavioral Sciences, Center for Psychedelic and Consciousness Research, Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [3 ]Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [4 ]Department of Psychological & Brain Sciences, Krieger School of Arts & Sciences, Johns Hopkins University, Baltimore, MD, USA
                Article
                10.1177/02698811231209194
                37947321
                d62565be-96bf-4548-9ba0-a1ce19e8b24b
                © 2023

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