July 19, 2023
Alison McInnes, MD, MS
The conference was a few weeks ago, but as we’ll explore today, in the world of psychedelic medicines, “you need to go slow to go fast.”
We’ll cover highlights about therapeutic effects and psychedelic law:
Without further ado, let's dive in:
Dr. Gul Dolen's work may suggest this is the case. Dolen's theory, which is fast gaining recognition, suggests that all psychedelics, from ketamine to MDMA, psilocybin, LSD, and ibogaine, act by reopening a critical period of social reward learning.
The fascinating part? The duration of the psychedelic experience is directly proportional to the length of this reopened learning period.
Here's how it works: Ibogaine, which has the longest psychedelic experience, also opens the longest learning period, which can have a profound effect on treating conditions such as addiction. While supervising lengthy sessions for ibogaine or LSD is challenging, the upside is that the patient wouldn't need to come into the clinic as often.
Conversely, while short-acting, non-psychedelic compounds being developed by some companies might seem attractive for their manageability, Dolen argues that they are likely less effective due to their brief action time.
What about ketamine, the only legal psychedelic-like substance for treatment-resistant depression?
While offering a shorter psychedelic experience, ketamine keeps the critical learning period open for a longer duration with repeated doses. This could explain its sustained effect, necessitating fewer maintenance treatments and making it an effective choice for treating treatment-resistant depression.
Adherence is a critical concern across psychiatry treatments; intravenous ketamine therapy is no exception.
Dr. McInnes and team examined a dataset of over 11,000 patients to determine which factors influence patients to adhere to treatment.
Here’s what they found:
1️) Approximately 45% of individuals have difficulty adhering to the minimum effective course of induction for KIT—defined as at least four infusions within 28 days.
2️) When patients successfully complete four or more infusions, they experience a significant reduction in depression and anxiety scores.
3️) The study showed that a clinic's rate of successful induction, the baseline severity of depression, and the number of patients previously treated at a clinic were predictors of adherence to intravenous ketamine therapy.
4️) Encouragingly, the research model can correctly predict adherence outcomes for 68% of patients—highlighting the potential to anticipate which individuals are more or less likely to adhere to treatments.
These findings are instrumental in helping to refine treatment strategies and enhance patient outcomes. They lay the foundation for the development of advanced clinical decision-support tools.
Now let’s talk about substance abuse and addiction, through the lense of ketamine and psilocybin:
Dr. Elias Dakwar regards ketamine as a "mirror molecule” based on a paradox:
How can ketamine, a substance to which people can become addicted, be used effectively to treat alcohol or cocaine use disorder? The answer, according to Dakwar, lies in context and therapeutic support.
This was showcased in a study led by Dakwar, where his team injected ketamine into volunteers dependent on cocaine. Interestingly, the day after the injection, when offered the opportunity to use cocaine in their lab, a greater number of volunteers who received ketamine refused the offer compared to those who received a control infusion.
When administered within a well-structured harm reduction environment, ketamine can indeed have a powerful effect on treating substance use disorders.
Psilocybin boasts a relatively intermediate duration of subjective experience (and according to Dr. Dolen, opening a relatively longer critical learning period), A single dose, accompanied by a robust support system, can yield effects lasting up to 12 weeks.
These results come from Dr. Bogenschutz' recently completed randomized controlled trial. This study demonstrated a significant decrease in alcohol craving, an improved affective tone, and enhanced executive control following psilocybin treatment.
Most intriguingly, an increased sense of self-compassion surfaced as the primary mediator of these positive responses. This approach, which humanizes and empathizes with the individuals undergoing treatment, stands in stark contrast to some conventional addiction programs, which can often focus on shame or unrealistic self-improvement.
As we continue to delve into the potential benefits of psychedelics, it's clear that self-compassion is vital in filling the void that addiction leaves behind.
Karen Luong from Husch Blackwell discussed the key legal challenges facing practitioners and businesses in the emerging field of psychedelics:
What are the main legal challenges facing practitioners and businesses in the emerging field of psychedelics?
Karen: Practitioners need to stay updated on regulatory changes at every level, including ethical rules from professional organizations. Businesses, while passionate, must remember that substances like psilocybin and MDMA are still federally illegal. Also, state laws may change rapidly, affecting business plans.
How does your law firm, Hush Blackwell, advise clients on the intersection of state and federal laws regarding psychedelics?
We emphasize caution. Though substances may be decriminalized, commercial laws might still be developing. Changes can happen quickly, impacting business investments. We also highlight the tax implications of running a state-legal but federally illegal business.
Can you share something you've learned or something that inspired you at the Psychedelic Science Conference?
Karen: The energy here is inspiring. It's wonderful to see a diverse group interested in learning about psychedelics. The accessibility of scientific talks to non-scientists is also commendable.
What are your hopes for the future of psychedelics and psychedelic law?
Karen: I hope the enthusiasm visible here can shift public perceptions. There's bipartisan support for psychedelics, and I believe we can revisit old prejudices and realize the potential of these substances to address societal challenges.
More in-depth conversation on navigating the legal maze surrounding psychedelics can be found in our upcoming podcast episode - be sure to subscribe to “Psychiatry Tomorrow” on your favorite podcast platform, and listen to the latest episode: Set, Setting, and the Healing Potential of Psychedelics with Andrew Penn, M.S., PMHNP.
That's all for now. As we tread new paths, remember: progress must be underpinned by thoughtful, ethical, and thorough research and practice—and the technology to enable it.
Here's to forging our way responsibly in the world of psychedelic psychiatry. We'll catch up soon with more insights from psychiatry's frontier.
Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O'Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S., & Worth, L. (2022). Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 79(10), 953–962. https://doi.org/10.1001/jamapsychiatry.2022.2096
Dakwar, E., Levin, F., Hart, C. L., Basaraba, C., Choi, J., Pavlicova, M., & Nunes, E. V. (2020). A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial. The American Journal of Psychiatry, 177(2), 125–133.
Dakwar, E., Nunes, E. V., Hart, C. L., Foltin, R. W., Mathew, S. J., Carpenter, K. M., Choi, C. J. J., Basaraba, C. N., Pavlicova, M., & Levin, F. R. (2019). A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. The American Journal of Psychiatry, 176(11), 923–930. https://doi.org/10.1176/appi.ajp.2019.18101123
Nardou, R., Sawyer, E., Song, Y. J., et al. (2023). Psychedelics reopen the social reward learning critical period. Nature, 618, 790–798. https://doi.org/10.1038/s41586-023-06204-3
*Dr. Elias Dakwar's meditation on the mirror molecule is from his presentations rather than cut-and-dry research publications.
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