Despite the oft-reported ineffability (the inability to adequately verbalize the phenomenological content of their experiences), respondents in several studies did offer rather detailed descriptions of their experiences, as well as reflections on the intervention. Not all studies described phenomenological aspects of the acute experience; this is most likely related to the specific methodology used or the researchers’ areas of interest. Participants also reported improved mood, greater optimism, an increased emotional repertoire, and positive emotional changes [53, 78, 82, 84]. In some cases, this included increased confidence in dealing with future adverse situations, such as a relapse in symptoms or the recurrence of their illness [53, 81]. Enhanced (inter)connectedness was reported across substances, both during sessions and afterwards, with respondents alluding to positive changes in friendships and improved relationships with family members [53, 78, 80].
Psilocybin eases existential anxiety in people with life
Furthermore, decreased amygdala cerebral blood flow correlated with reduced symptoms in the same study (Carhart-Harris et al., 2017). The same patients showed increased amygdala reactivity the morning after psilocybin and a reduction in amygdala, PFC connectivity in response to fearful faces (Roseman et al., 2018; Mertens et al., 2020). These results are surprising given that decreased amygdala reactivity and increased amygdala-PFC connectivity under the acute influence of psychedelics have been shown to correlate with positive mood in healthy participants (Kraehenmann et al., 2015; Mueller et al., 2017; Bershad et al., 2019). It has to be noted, however, that increased amygdala reactivity in depressed patients was measured before any psychological or psychotherapeutic interventions aiming at integrating the psychedelic experience (Roseman et al., 2018). It is therefore conceivable that psilocybin facilitated the processing of negative life events, leading to markedly increased emotional processing and amygdala reactivity the morning after the session.
Reclassification recommendation for psilocybin
At this time, countercultural forces combined with the rise of psychopharmacology to fuel optimism about psychedelic therapies. Between the 1950s and 1970s, psychedelics like lysergic acid diethylamide (LSD) and psilocybin were given to tens of thousands of patients to treat conditions like alcohol abuse, depression, anxiety, and end-of-life distress [9]. Research into these substances largely halted once the Nixon administration placed them on schedule 1 of the Controlled Substances Act of 1970, where they remain to this day.
What Is Psychedelic Therapy?
The literature addressing the effects of psychedelics on rodent behaviors relevant to psychiatric and cognitive function is sparse, and results of different studies may appear to align or to conflict with each other without being truly comparable. Further investigation found that a single dose of psilocybin (1 mg/kg) or LSD (0.15 mg/kg) profoundly affected long-term behavioral measures of male Wistar-Kyoto rats in a time- and context-dependent way (Hibicke et al., 2020). Time intervals between dosing and behavioral testing is another factor influencing the results of studies with psychedelics. As in humans, “set and setting” seems to play a role in the long-term behavioral outcome of rodents given psychedelics. Meanwhile, 2016 brought a pair of double-blind, randomized controlled clinical trials with a total of 80 patients that looked at psilocybin-assisted psychotherapy’s effects on anxiety and depression in patients with life-threatening cancer [28•, 29•].
Researchers observed a significant reduction in symptoms for the first 5 weeks following treatment. At 5 weeks, nine participants had responded to treatment, and four had depression that was in remission. Participants were more likely to have improvements in their depression symptoms if they had quality psychedelic experiences are psychedelics addictive during the drug dose. Social and legal hurdles, barriers to access and scientific questions make it unlikely that psychedelics will replace current mental health treatments, many experts agree. More likely is that with enough research, psychedelic substances will become another tool for doctors and therapists.
In the 1970s, MDMA was used alongside talk therapy, as it was thought to enhance communication. In the 1990s, MDMA was studied for its potential pain-relieving effects in terminally ill patients (although the results of the studies were not released). A Schedule I drug, LSD (lysergic acid diethylamide), or acid, was first created in 1938 in Switzerland. LSD is known for facilitating a “trip” experience, which can involve hallucinations and “spiritual or mystical experiences” potentially involving visions, auditory distortions and a disjointed sense of space and/or time. LSD can be ingested through absorbent paper, tablets, saturated sugar cubes or via liquid form. Before a session, the provider should prepare you for the experience, including explaining what you might feel or what you may want to work on mentally or emotionally while feeling the drug’s effects.
The Future of Psychedelic Medicine for Mental Illness
- It is possible that the altered integration of sensory perceptions facilitates a novel experience of the self and its environment and may help to reduce rigid or ruminative thinking patterns as observed in psychiatric disorders.
- This article aims to address this lacuna by presenting an overview of the available qualitative research.
- Compounds able to cross into the neurons and bind to these inner receptors induced the formation of dendritic spines.
- Any drug-specific side effects are best discussed with the professional overseeing one’s session.
Remarkably, decreased drug, alcohol, and medication use were also reported in studies with MDMA, ayahuasca and psilocybin that did not deal directly with substance use [53, 80, 87]. Mystical, religious or spiritual aspects of healing were widely reported in patients’ healing experiences in treatment with ayahuasca [88, 90], ibogaine [79, 86], and psilocybin [53, 81–83], as well as for different mental disorders. These were related to transpersonal experiences, feelings of awe and transcendence, a dissolving of the self, a connection to greater forces, an interconnectedness with all life, and the unity of all and everything.
Furthermore, both HNK enantiomers [(2S,6S)- and (2R,6R)-HNK] exerted dose-dependent antidepressant actions in several rodent tests (Zanos et al., 2016; Yang et al., 2017; Pham et al., 2018). Interestingly, (2R,6R)-HNK, the enantiomer with the stronger antidepressant-like effects, is a less potent antagonist of NMDAR than ketamine itself (Moaddel et al., 2013; Zanos et al., 2016, 2017; Morris et al., 2017; Suzuki et al., 2017). Because of its reduced effects at the NMDAR, (2R,6R)-HNK did not induce NMDAR inhibition-mediated side effects, such as sensorimotor dissociation (Zanos et al., 2016). However, (2R,6R)-HNK does not appear to be as potent as ketamine in relieving the behavioral changes induced by chronic social defeat in mice (Yang et al., 2017), suggesting the involvement of both NMDAR-dependent and -independent pathways. Ketamine induces both synaptic and structural plasticity in the hippocampus, mPFC, and lateral habenula (Li et al., 2010, 2011; Yang et al., 2018b; Moda-Sava et al., 2019), involving signaling pathways that control protein synthesis (Li et al., 2010; Autry et al., 2011), such as the mTORC1 pathway. Indeed, increasing evidence suggests that activation of mTORC1 is a critical mechanism underlying the antidepressant action of ketamine and its metabolite (2R,6R)-HNK (Workman et al., 2018; Zanos and Gould, 2018).
Critical Appraisal of Study Quality
- It’s thought that people get “stuck” because the brain is designed to be good at developing habits, said Chris Tuell, a professor of psychiatry and behavioral neuroscience and director of addiction services at the University of Cincinnati’s College of Medicine.
- In many cases, doctors try this form of therapy on people whose symptoms have not responded well to standard medications or therapies.
- Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.
- Another study microdosed some rats with psilocin (another psychoactive component of magic mushrooms) and others with a different psychedelic called ketamine, and found both to mildly alleviate anxiety in rats experiencing a stressful maze.