09 Nov Therapeutic effect of psilocybin in addiction: A systematic review PMC
In the late 1990s, the US Drug Enforcement Administration (DEA) permitted some researchers to study limited amounts of psychedelics, which allowed research to resume. Clinical trials have now been conducted at leading universities, and a growing body of evidence supports the use of psychedelics, such as psilocybin and MDMA, in the treatment of depression2, post-traumatic stress disorder3 and anxiety toward the end of life4. No studies were identified evaluating the efficacy of psilocybin in patients with benzodiazepines or hypnotics, caffeine, cannabis, hallucinogens, ketamine, inhalants or other (or unknown) substances use disorder, nor in patients with a gambling or gaming disorder. Researchers point to two characteristics that make psilocybin an especially attractive potential treatment for mental health conditions. First, while it can trigger some dangerous side effects if not used in a controlled environment, it tends not to be addictive. Second, psilocybin can have long-lasting effects, which means people would only have to take it intermittently, putting them at a reduced risk from any side effects.
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In addition, many trials evaluating the efficacy of psilocybin in SUDs have been started since 2016, some of which may already have been published and not yet included in previous systematic reviews. Our aim was to assess the efficacy of psilocybin in patients with SUD and non-substance-related disorders. Psychedelic-assisted therapy e.g., with lysergic acid diethylamide (LSD) has shown promising results as treatment for substance use disorders (SUDs).
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- Classic psychedelics (e.g., psilocybin, LSD), which are also all essentially potent hallucinogens, act primarily as agonists at 5HT2A receptors resulting in activation of cortical pyramidal neurons and downstream glutamate release.
- Our search strategy was strengthened by including review of studies selected from three research databases, namely PubMed, Cochrane, and EBSCOhost, and screening for the best level of evidence available for our question (i.e., randomized human trials).
- She had started with a low dose, and subsequent higher doses worsened her symptoms consisting of altered visual perceptions including tracers, trails, halos, and visual drifting.
- Given the higher prevalence of cannabis use and CUD in those with PTSD compared to the general population (42), it should be anticipated that MDMA could be therapeutically administered in persons with co-morbid disorders.
We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes. The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model.
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Limited aetna momentum program data and reporting are available on the use of psychedelics in persons with CUD, and more research is needed given the anticipated increase in CUD incidence and increasing interest in psychedelic use. While psychedelics, broadly, have a high therapeutic index with infrequent serious adverse effects, particular adverse effects at risk in the CUD population, such as psychosis and cardiovascular events, should be considered. Under existing regulation, well-capitalized private companies fund most research and, to a large extent, they control the agenda and shape federal drug policies.
The therapeutic effects from these experiences can be enduring, and it is conceptualized that during the psychedelic experience a therapeutic window in the mind is temporarily opened which facilitates gained insight and emotional release. In conjunction with psychotherapeutic support, this insight can potentially lead to a healthy revision of outlook and lifestyle (47). Finding long-lasting treatment options for mental health disorders, including addiction, is complicated and met with various challenges. The use of psychedelics in treatment is getting more attention as recent research suggests efficacious treatment outcomes in specific behavioral health disorders.
Our study is limited by the search strategy’s focus on clinical research, which likely contributed to the exclusion of potentially relevant articles based on self-report surveys (e.g., Kuc et al., Garcia-Romeu et al.). Additionally, our search did not include literature focused on individuals who use MDMA heavily and also use cannabis because of the lack of relevance to the study. However, future evaluation of this population might provide insight into comorbid use and potential complications of MDMA and cannabis co-use. Our search revealed a significant gap in the clinical research literature, as no organized studies assessing psychedelics in those with CUD have been reported. This limitation impacts both the effort to identify novel and needed treatments for CUD, and the understanding of safety considerations in utilizing psychedelic treatments in those with CUD or at risk for CUD, such as individuals who use cannabis heavily or regularly. As psychedelics are currently being studied for other SUDs, we have examined the literature to explore possible rationales for the mechanism, utility, and safety for their use in CUD.
In another review, no incidences of prolonged psychotic reactions or precipitations or schizophrenia spectrum disorders were identified out of 110 subjects. However, one experienced symptom of emotional instability, anxiety, and depression which lasted for several weeks. A few subjects described mood swings, “excessive pensiveness and introversion” and memory/concentration issues after the drug session, which generally resolved after a few weeks (69). The risk of HPPD, as illustrated in the case report, is considered rare and the incidence incompletely known. While the use of psychedelics at therapeutic doses in supportive environments decreases the risk for acute or prolonged psychosis, the added vulnerability for psychosis in those with chronic cannabis use should add a layer of enabling vs supporting caution. Low, medium, and high doses were assigned in that order, with a very low dose inserted randomly after the first low dose.
Her first psychotic symptoms began following her initial use and she began to reexperience persisting symptoms of LSD intoxication immediately afterward. She had started with a low dose, and subsequent higher doses worsened her symptoms consisting of altered visual perceptions including tracers, trails, halos, and visual drifting. She was admitted to a psychiatric inpatient unit 2 months after her last use of LSD following an intentional overdose of acetaminophen and ibuprofen. She had no contributory family history and her physical exam and labs, includeing urine drug screen, were unremarkable. She was diagnosed with HPPD, defined as episodic re-experiencing of hallucinations and mimicking acute hallucinogen intoxication following prior, but not recent, hallucinogen use; and specified as Type 2, which has more intense symptoms and more episodes with longer durations than Type 1, which is more self-limiting. Risperidone yielded significant improvement in her symptoms of psychosis but had no effect on those of HPPD (36).
The schedule I status of most psychedelics imposes a ceiling on many policy recommendations. The evidence in support of rescheduling is strong, particularly for psilocybin, which is derived from fungi5. Unlike other schedule I substances such as heroin, do you need to wean off prozac and schedule II compounds, including cocaine and fentanyl, psilocybin exhibits a low risk of toxicity and a very low potential for dependence or addiction6. Psilocybin use is not criminalized in several countries, including Portugal and the Netherlands, and a study commissioned by the Dutch Ministry of Health found that over-the-counter sales posed minimal risk to individual people and the public7. Psychedelics are a class of natural and synthetic compounds that includes psilocybin, MDMA (3,4-methylenedioxymethamphetamine), ibogaine and DMT (dimethyltryptamine).