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Neurotherapeutics : the Journal of the... Jul 2017Psilocybin and other 5-hydroxytryptamine agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century... (Review)
Review
Psilocybin and other 5-hydroxytryptamine agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.
Topics: Hallucinogens; Humans; Mental Disorders; Psilocybin
PubMed: 28585222
DOI: 10.1007/s13311-017-0542-y -
Psychiatry Research Feb 2020The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms.... (Meta-Analysis)
Meta-Analysis Review
The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms. Across four studies (one uncontrolled; three randomized, placebo-controlled; N = 117), within-group pre-post and pre-follow-up effects on anxiety and depression were large (Hedges' gs=1.16 to 1.47) and statistically significant. Across three placebo-controlled studies, pre-post placebo-controlled effects were also large (gs = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. Limitations include the small number of studies and risk for bias within studies. Results tentatively support future research on psilocybin for the treatment of anxiety and depression.
Topics: Anxiety; Depression; Female; Humans; Male; Psilocybin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31931272
DOI: 10.1016/j.psychres.2020.112749 -
Neuropharmacology Jan 2023Mescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid... (Review)
Review
INTRODUCTION
Mescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited.
OBJECTIVES
This article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research.
FINDINGS
Mescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting.
CONCLUSION
The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings. This article is part of the Special Issue on 'Psilocybin Research'.
Topics: Animals; Humans; Mescaline; Hallucinogens; Psilocybin; Lysergic Acid Diethylamide; Serotonin 5-HT2 Receptor Agonists; Memory Disorders
PubMed: 36252614
DOI: 10.1016/j.neuropharm.2022.109294 -
Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders.Molecules (Basel, Switzerland) Apr 2022The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had... (Review)
Review
The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had been conducting research on lysergic acid diethylamide (LSD) at the time. Psychedelic drugs such as ,-DMT/DMT (,-dimethyltryptamine), 5-MeO-DMT (5-methoxy-,-dimethyltryptamine), LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxymethamphetamine) and psilocybin have had significant value as an entheogen in spiritual, religious (shamanic) and sociocultural rituals in Central and South American cultures for thousands of years. In the 1960s, the globalization of these drugs and their subsequent spread outside of their indigenous, old-world cultures, led to the subsequent implementation of strict drug control laws in many Western countries. Even today, psychedelics are still classified as Schedule I drugs, resulting in a still lingering negative stigmatization/perception, vilification, and ultimate criminalization of psychedelics. This controversy still lingers and still limits scientific research and full medical acceptance. For many years up until recently, the spiritual, religious and medicinal value of these drugs could not be explored in a scientific context. More recently, a second wave of psychedelic research is now focusing on psychedelics as neuropharmaceuticals to treat alcohol and tobacco addiction, general mood and anxiety disorders and cancer-related depression. There is now a vast array of promising evidence-based data to confirm the years of anecdotal evidence of the medicinal values of psychedelics. Natural therapeutic alternatives such as psychedelic drugs may provide a safe and efficacious alternate to conventional drugs used to treat mood and anxiety disorders. In a Western context in particular, psychedelic drugs as therapeutic agents for mood and anxiety disorders are becoming increasingly of interest amidst increasing rates of such disorders globally, changing social constructions, the implementation of government regulations and increasing investment opportunities, that ultimately allow for the scientific study to generate evidenced-based data. Alternative psychotherapeutic interventions are gaining interest also, because of their low physiological toxicity, relatively low abuse potential, safe psychological effects, and no associated persisting adverse physiological or psychological effects during and after use. On the other hand, conventional psychotic drugs and anti-depressants are becoming less favorable because of their adverse side effects. Psychedelic neuropharmaceutical interventions may with medical oversight be the solution to conventional psychiatric disorders such as depression and anxiety, and an alternative to conventional psychiatric treatment options. This paper will review the therapeutic potential of psychedelic drugs as alternative therapeutic options for mood and anxiety disorders in a controlled, clinical setting, where the chances of adverse psychological episodes occurring are mitigated.
Topics: Anxiety Disorders; Hallucinogens; Humans; Lysergic Acid Diethylamide; N,N-Dimethyltryptamine; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin
PubMed: 35458717
DOI: 10.3390/molecules27082520 -
Neuropsychopharmacology : Official... Oct 2017Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a... (Review)
Review
Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.
Topics: Animals; Hallucinogens; History, 20th Century; History, 21st Century; Humans; Mental Disorders; Psilocybin
PubMed: 28443617
DOI: 10.1038/npp.2017.84 -
Journal of the Neurological Sciences Sep 2022Existing pharmacological treatments for psychiatric disorders have demonstrated limited efficacy, delayed onset of action, and significant burden of side effects. Recent... (Review)
Review
Existing pharmacological treatments for psychiatric disorders have demonstrated limited efficacy, delayed onset of action, and significant burden of side effects. Recent findings from human studies with psychedelics have shown promise, demonstrating rapid and sustained clinical benefits of these compounds for a variety of psychiatric disorders. Classical psychedelics have a rich history and some of these compounds have been used in shamanic and spiritual ceremonies for millennia. The psychoactive effects of these drugs, particularly on human consciousness, have generated great scientific curiosity, and early research on psychedelics suggested their clinical benefits for psychiatric conditions, including alcohol use disorders and anxiety and depressive symptoms in terminal illness and life-threatening conditions. Since the 1990s, after a period of dormancy that followed the criminalization of psychedelic drugs since the Controlled Substance Act of 1970, the continued interest in their unique psychoactive effects along with the pursuit for novel and more effective treatments in psychiatry have led to a renewed interest in research on these compounds. While preliminary findings on psychedelics are encouraging, current evidence is still insufficient to support extensive use of these drugs routinely. Long-term safety and efficacy of these compounds remain unclear, and several clinical trials are underway and may add clarity to these questions. Therefore, this article intends to provide an overview of the evidence to date on psychedelic drugs - particularly psilocybin, MDMA, and LSD - for the treatment of psychiatric disorders.
Topics: Alcoholism; Hallucinogens; Humans; Lysergic Acid Diethylamide; Mental Disorders; Psilocybin
PubMed: 35841696
DOI: 10.1016/j.jns.2022.120332 -
Pain Apr 2023Psychedelic serotonergic agonists such as psilocybin have recently been shown to produce sustained benefit in refractory depression, end of life anxiety, and addiction...
Psychedelic serotonergic agonists such as psilocybin have recently been shown to produce sustained benefit in refractory depression, end of life anxiety, and addiction when administered in hallucinogenic doses and coupled with psychotherapy. Although it has been suggested that similar high-dose protocols may help chronic pain conditions, there are few published clinical trials of psychedelics for pain. The use of these agents in subpsychedelic doses for chronic pain management has received even less attention. This case series details the experiences of 3 individuals who have used low-dose psilocybin to manage chronic neuropathic pain. Although the nature and etiology of each patient's pain vary, they share a common experience, including inefficacy of current therapeutics and decreased quality of life. Through self-administration of psilocybin, these patients have achieved robust pain relief with decreased reliance on traditional analgesic medications. Despite varying preparations and uncertain potencies, the analgesic effects for all 3 patients occurred at doses without a psychedelic experience and with minimal cognitive or somatic adverse effects. Furthermore, the efficacy of pain relief and, in some cases, the duration of the effect were magnified when coupled with functional exercise. In addition, in 1 case, repeated dosing seemed to produce increased relief, suggesting a possible long-term plasticity-mediated effect. These commonalities highlight psilocybin's therapeutic potential in the treatment of chronic pain that warrants further investigation.
Topics: Humans; Psilocybin; Hallucinogens; Chronic Pain; Quality of Life; Chronic Disease; Analgesics
PubMed: 36066961
DOI: 10.1097/j.pain.0000000000002778 -
Translational Psychiatry Aug 2022The use of low sub-perceptual doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated... (Randomized Controlled Trial)
Randomized Controlled Trial
The use of low sub-perceptual doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.
Topics: Agaricales; Double-Blind Method; Hallucinogens; Humans; Motivation; Psilocybin
PubMed: 35918311
DOI: 10.1038/s41398-022-02039-0 -
The New England Journal of Medicine Nov 2022
Topics: Humans; Depression; Depressive Disorder, Treatment-Resistant; Hallucinogens; Psilocybin
PubMed: 36322849
DOI: 10.1056/NEJMe2210975 -
Journal of Psychopharmacology (Oxford,... Jul 2023Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses. However, methodological limitations (e.g., placebo-control, blinding) limit interpretability of the existing literature.
METHODS
In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe major depressive disorder were administered placebo ( = 19) followed by psilocybin (0.3 mg/kg) ( = 15) 4 weeks later. Dosing sessions were embedded within an manualized course of psychotherapy. Enhanced blinding procedures were used. Depression, anxiety, and quality of life were measured over a 16-week study period.
RESULTS
Depression and anxiety significantly improved following both placebo and psilocybin with no significant difference in the degree of change between the two conditions. However, antidepressant effect sizes were larger after psilocybin (' = 1.02-2.27) than after placebo (' = 0.65-0.99) and there were high rates of response (66.7%) and remission (46.7%) following psilocybin administration. Antidepressant effects following psilocybin persisted, on average, for 2 months and there were persisting improvements in mood-related quality of life domains. The strength of mystical-type experience during psilocybin dosing was not correlated with subsequent antidepressant effects.
CONCLUSIONS
The results of this exploratory study highlight the complex interplay between expectancy, therapy effects, and drug/placebo effects in psychedelic-assisted psychotherapy studies. Nonetheless, the acute and persisting clinical improvements observed following psilocybin support further study of its potential in the treatment of major depression. Future studies should more explicitly mitigate and measure expectancy effects and assess the impact of repeated dosing and different forms of psychotherapeutic support.
Topics: Humans; Antidepressive Agents; Depressive Disorder, Major; Hallucinogens; Psilocybin; Quality of Life
PubMed: 36938991
DOI: 10.1177/02698811231154852