Could treatments with drugs like ketamine or psilocybin be helpful for people struggling with severe mental health issues? Psychiatrist Ben Lewis, MD, with Huntsman Mental Health Institute, navigates the potential path of psychedelic medicine from taboo to treatment. Learn about the clinical and therapeutic use of psychedelics in mental health, examining how they can provide significant relief for conditions that are difficult to address with conventional treatments. While the beneficial effects of psychoplastogens can last for months following a single administration (40, 166, 167), and these medicines have demonstrated efficacy across a range of neuropsychiatric disorders including depression, PTSD, and addiction (156, 168–172), they are not panaceas. Their broad therapeutic utility likely arises from their ability to impact the structure/function of layer V pyramidal neurons in the PFC. As the PFC is a key hub impacted in most neuropsychiatric disorders, it is not surprising that psychoplastogens have proven useful for a variety of indications.
The therapeutic potential of psychedelic drugs: tempered optimism (RLC-H)
More recently, clinical trials testing some of the predictions derived from NMDAR-based models have yielded unexpected results (Costi et al., 2019; Abdallah et al., 2020). Concerning the mTORC1 pathway, for example, a recent clinical study demonstrated that peripheral coadministration of rapamycin to treatment-resistant MDD patients enhanced, rather than blocked, the antidepressant effect of ketamine (Abdallah et al., 2020), suggesting a more complex interaction between these drugs in humans. In mice subjected to social defeat stress, optogenetic stimulation of the ventral medial PFC increased social interaction and reduced anhedonia as measured via the sucrose preference test (174). Deisseroth et al. later found that optogenetic stimulation of medial PFC neurons projecting to the dorsal raphe nucleus (DRN) decreased immobility in the forced swim test (175). The forced swim test is a preclinical assay for antidepressant potential with high predictive validity (176, 177), and activation of this PFC → DRN circuit likely mediates the robust effects of psychoplastogens on forced swim test behavior.
3.1. Single‐Cell Transcriptome
A statistically significant odds ratio greater than one indicates an association, and an odds ratio less than one indicates an inverse association. Because the mental health outcomes are all relatively uncommon, in this case, the odds ratio is a close approximation to the relative risk. For example, an adjusted odds ratio of 0.6 for a given are psychedelics addictive outcome indicates that the rate of that outcome in psychedelic users is approximately 60% the rate in non-psychedelic users, after adjusting for control variables. Psychedelic therapy must also overcome the stigma that surrounds both psychedelic drugs and mental health, which will take time and education, explains Nicholson. Medical professionals, insurance companies and regulatory bodies, both state and federal, will also have to back the therapy to improve accessibility.
- 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).
- Depression and related neuropsychiatric diseases are often viewed as stress-related disorders given the fact that they can be precipitated or exacerbated by chronic stress (43).
- We did not find use of psychedelics to be an independent risk factor for mental health problems.
- “Psychedelics have already arrived in society as an accepted fact,” said German financier Christian Angermayer, who has helped fund research into how psychedelics could treat mental health conditions.
Phenomenology of the Psychedelic Experience
Across the board, respondents in these studies describe positive and often lasting changes in quality of life and well-being 78, 82, 85, experiencing an increased sense of peace and mental space in daily life 53, 81, 84. Increased appreciation of beauty in art, music, and nature was reported by several participants 53, 83. “Emotionally it was a roller coaster ride … The first time it was very brutal, painful, at least emotionally very painful.
Use of psychedelics increased in the 1960s and has remained widespread in many parts of the world ever since. Over 30 million people living in the US have used lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline (peyote and other cacti) 4. Common reasons for using psychedelics include mystical marijuana addiction experiences, curiosity, and introspection 5.
In contrast, the mood-elevating properties of psilocybin seem to last significantly longer (40–42, 151), as do its effects on neuronal structure (152). Currently, it is unclear exactly how long the effects of non-hallucinogenic psychoplastogens will last following a single administration, and head-to-head comparisons with ketamine and psilocybin are warranted to help establish optimal dosing frequency. Psychoplastogens produce robust, fast-acting, and long-lasting effects on structural plasticity in the PFC. This may explain why they have demonstrated efficacy in many preclinical rodent behavioral tests involving PFC circuitry including the forced swim test and fear extinction learning (151, 194–197).
Percentage of patients excluded from recent large MDD trials of the hallucinogenic drug psilocybin and the non-hallucinogenic drug vortioxetine. For additional information on the broad range of smaller trials with psychedelics, please see (262, 263). One of the most important questions to address is the durability of psychoplastogen effects. In both humans and rodents, the antidepressant responses of ketamine appear to last for about 1 week. This correlates well with the effects of the drug on dendritic spine density (129, 150).
MDMA‐assisted therapy alleviated severe PTSD after FDA‐approved first‐line drugs sertraline and paroxetine treatment. It can induce psychedelic effects including vivid imagery, and “mystical and peak” experiences. Ketamine can be administered via intramuscular injection or intravenously, or ingested as a powder, lozenge or nasal spray. O’Donnell says she https://genechavezphotography.com/2024/08/13/how-to-get-sober-and-stay-sober-2/ envisions specialized psychedelic clinics popping up in areas around the country where patients will receive guidance, support, and psychotherapy along with psychedelic treatment.
