If participants know they have received the psychedelic treatment they already believe will improve their symptoms, this alone can improve clinical outcomes (i.e., the placebo effect) (67). It is important to note, however, that studies such as this are based on self-reports by people who have taken psychedelics in the past. In order to determine if psychedelic therapy is truly effective in the treatment of alcohol and substance use disorders, more research using randomized clinical trials is needed. Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) compared to an active placebo (e.g. a very low dose of the same drug) may reduce anxiety and depression. However, our confidence in the effect estimate is limited; we may find that the true effect is substantially different when more studies are conducted. Psychedelic-assisted therapy with classical psychedelics may reduce existential distress, but the evidence is mixed and very uncertain.
Of note, psilocybin remains a Schedule I drug, although as of February 2024, Australia, the states of Oregon and Colorado, and the Canadian state of Alberta have legalized psilocybin for medicinal purposes in supervised settings. Similar bills are currently underway in the states of California, Washington, New Jersey, and Massachusetts. The FDA has been reviewing the evidence for P-AT for mental health treatment, which may lead to legalization of P-AT for this purpose (38). Traditional buy lsd vial liquid medications for mental health conditions often take several weeks to become effective, or may only work for as long as a person takes them. Most research on psychedelic therapy, by contrast, has found an immediate improvement, often with a single dose. Psychedelic therapy is the use of plants and compounds that can induce hallucinations to treat mental health diagnoses, such as depression and post-traumatic stress disorder (PTSD).
See NIDA-funded projects related to psychedelic and dissociative drugs, and learn more about related clinical trials. Studies by Humphry Osmond, Betty Eisner, and others examined the possibility that psychedelic therapy could treat alcoholism (or, less commonly, other addictions). Bill Wilson, the founder of Alcoholics Anonymous, used LSD during supervised experiments with Betty Eisner, Gerald Heard, and Aldous Huxley. With Wilson’s invitation, his wife Lois, his spiritual adviser Father Ed Dowling, and Nell Wing also participated in experimentation of this drug. Later Wilson wrote to Carl Jung, praising the results and recommending it as validation of Jung’s spiritual experience.52 According to Wilson, the session allowed him to re-experience a spontaneous spiritual experience he had had years before, which had enabled him to overcome his own alcoholism. In vivo molecular neuroimaging in the living human brain has been made possible by the advent of PET and Single Photon Emission Computed Tomography (SPECT).
Conversely, if participants know they received a treatment they already believe is unlikely to improve their symptoms, e.g., an inert placebo, this alone can worsen outcomes (68,69). Use of “active” placebos that mimic aspects of the psychedelic experience is essential, as is the use of masked assessors. The adequacy of masking for both patients and providers should be assessed, along with patients’ treatment expectations before treatment.
The PFC has long been implicated in addiction with models such as Impaired Response Inhibition and Salience Attribution (IRISA) which summarizes the dysfunction of this brain region (113) and identifies it as a target to test novel treatments. As such, these imaging paradigms can feasibly be adopted into studies of the effects of psychedelics on addiction processes related to dysfunctional executive and cognitive control mediated by PFC-striatal connectivity. Importantly, participants were often aware of the treatment they were receiving, which may influence their results. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing. Two recent randomized placebo-controlled phase 3 trials of the Lykos MDMA-AT protocol have demonstrated treatment efficacy with large effect sizes.
The situation is arguably worse for individuals with other substance or behavioral addictions, which have fewer or no clinically efficacious medications available (11). Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) compared to an active placebo may improve quality of life and induce spiritually significant experiences, but the evidence is very uncertain. A recent meta-analysis on the effects of P-AT on anxiety and depression showed large and statistically significant reductions of anxiety (60). In the placebo-controlled studies included in the meta-analysis, these results were maintained, indicating the therapeutic potential of psilocybin for treating anxiety and depression. Although there is currently no published data on psilocybin use for treating PTSD, the strong impact of psilocybin on conditions that often co-occur with PTSD, such as depression and anxiety, indicates the potential beneficial impact of the psilocybin augmented PTSD treatment. People with eating disorders often experience other mental health symptoms, so psychedelic therapy might ease the symptoms that lead to disordered eating.
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