David Connell
Paloma Lehfeldt, MDIf someone were to tell you they’ve been using LSD for anxiety, what would you think? You probably wouldn’t expect that LSD, a powerful psychedelic drug most associated with the counterculture movement of the 1960s-1970s, would be a legitimate candidate in the search for new ways to treat generalized anxiety disorder.
But new research is changing that.
Lysergic Acid Diethylamide (LSD), often called “acid,” is a psychedelic drug known for its potent psychological effects. It was discovered in 1938 by Swiss chemist Albert Hofmann while studying ergot, a fungus that grows on rye. LSD’s journey from a Swiss lab in 1938 to clinical trials today is as colorful as its hallucinogenic reputation. Several studies highlighted the promise of LSD-assisted psychotherapy significantly reducing anxiety levels in participants. Yet, these trials also unveiled challenges tied to its psychedelic nature, showing that while the therapeutic potential is compelling, the path to clinical acceptance is still being paved.(1, 2, 3, 4)
Recent Clinical Trials Explore LSD for Anxiety
Recently, a Phase II clinical trial explored the effectiveness of LSD coupled with psychotherapy to alleviate anxiety, yielding promising results. Participants were administered LSD and exhibited significant reductions in anxiety symptoms compared to those given a placebo for up to 16 weeks. These findings provide promising results for the treatment of anxiety symptoms in the short term, but more studies need to be conducted to observe how LSD impacts these same symptoms after a longer amount of time.(1)
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A literature review examining both the preclinical and clinical data related to LSD for the treatment of anxiety disorders suggests that even though LSD may temporarily increase anxiety, in the long term, it does induce anti-anxiety effects. This factor warrants consideration in therapeutic settings.(2)
Looking at other, more specific scenarios, a double-blind, randomized, active, placebo-controlled pilot study explored LSD-assisted psychotherapy in 12 patients grappling with anxiety associated with life-threatening diseases. The study aimed to study the effects of LSD-assisted psychotherapy in this particular population. The results of this pilot study indicated that in this setting, LSD may reduce anxiety.(3)
Yet another study looked at the effects of LSD administration to certain brain areas in mice subjected to chronic stress. The results of this study found that a higher dose of LSD given for a week did have the ability to stop the stress-induced behavior in the mice. Although this study was conducted in non-human research subjects, it may aid scientists in understanding the mechanism of LSD’s effect on anxiety.(4)
Ultimately, there is a growing body of evidence that suggests LSD has potential as a treatment for anxiety in some individuals, especially when combined with psychotherapy. The exploration of LSD’s efficacy across diverse anxiety-related scenarios, from generalized anxiety disorders to anxiety associated with severe illnesses, underscores the psychedelic’s versatile potential in mental health interventions.
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→How Can LSD Help With Anxiety?
It’s important to note that research is still in its early stages. That said, the available scientific literature indicates that LSD may impact anxiety in the following ways:(1, 2, 3, 4, 5)
Enhanced Emotional Insight:
LSD may facilitate heightened emotional insight and self-reflection. This awareness can help individuals explore and address the underlying issues contributing to their anxiety, fostering a deeper understanding and potential resolution.(6)
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Psychotherapeutic Synergy:
LSD may help create a conducive environment for therapy. Breaking down usual thought patterns and promoting a sense of connectedness may facilitate a more open and dialogue between the individual and the therapist.(7)
Neuroplasticity Promotion:
Psychedelics like LSD have been found to promote neuroplasticity, the brain’s ability to reorganize and form new neural connections. This enhanced neuroplasticity can potentially aid in reconditioning the brain’s response to stressors, thereby reducing anxiety symptoms.(8)
Ego-Dissolution
LSD may induce states of ego-dissolution, where one’s sense of self is temporarily altered or diminished. This can lead to a sense of unity and interconnectedness with others and the world, which might help alleviate feelings of isolation or existential anxiety often associated with chronic anxiety disorders.(9)
Mindfulness and Present-Moment Awareness:
The altered states of consciousness induced by LSD can foster mindfulness or present-moment awareness, which is often a core aspect of anxiety reduction techniques.(10)
Altering Fear-based Thought Patterns:
LSD, like all psychedelics, is an extremely powerful compound and demands respect and care. Using LSD outside of a controlled setting should only be done after extensive research and education. Furthermore, if one is using LSD in a recreational setting or for self-growth, it is a good idea to have a responsible, sober person (known as a tripsitter) on hand to help you through any difficult moments.
LSD, like all psychedelics, is an extremely powerful compound and demands respect and care. Using LSD outside of a controlled setting should only be done after extensive research and education. Furthermore, if one is using LSD in a recreational setting or for self-growth, it is a good idea to have a responsible, sober person (known as a tripsitter) on hand to help you through any difficult moments.
Current Clinical Trials Exploring LSD for Anxiety
The resurgence of interest in psychedelic substances for mental health treatment has propelled LSD into the clinical trial arena, particularly concerning anxiety disorders. A range of ongoing and active trials are investigating the therapeutic efficacy and safety of LSD in alleviating anxiety symptoms. For instance, a noteworthy Phase IIb trial under the moniker MM-120, spearheaded by Mind Medicine Inc., has been greenlit by the FDA to explore the impact of LSD on individuals diagnosed with Generalized Anxiety Disorder (GAD). Another Phase IIb dose-optimization trial examines the dosing process, employing a novel (salt-based) form of LSD as a potential treatment for GAD.
Some Active or Recruiting LSD Clinical Trials:
LSD for Anxiety Phase IIb Trial:
This trial aims to explore the efficacy of LSD as a treatment options for anxiety associated with Severe Somatic Diseases or in Psychiatric Anxiety Disorders.(12)
Phase IIb Dose-Optimization Trial:
Another Phase IIb dose-optimization trial commenced on August 25, 2022, where the first patient was dosed with a pharmaceutically optimized form of LSD for treating Generalized Anxiety Disorder.(13)
LSD-Assisted For Major Depression Trial:
In a clinical trial, LSD-assisted psychotherapy researchers are exploring LSD’s ability to treat end-of-life related anxiety.(14)
The current clinical trials are paving the way for LSD to transition from a stigmatized recreational drug to a potential therapeutic ally. With each meticulously designed trial, the scientific community is peeling back layers of uncertainty surrounding LSD, unveiling its potential in a controlled, clinical setting. For instance, the dose-finding study of MM-120 strives to pinpoint the precise dosage where the benefits outweigh the risks, a crucial step for any drug on the path toward clinical acceptance. Exploring LSD-assisted psychotherapy reflects an innovative approach, merging the traditional with the psychedelic to unlock new treatment modalities for anxiety.
Highlighting new scientific findings, like those here, is about more than finding new treatments for conditions like anxiety, it’s about changing the narrative around LSD, redefining its role, and broadening the horizon of human knowledge. As clinicians delve deeper and more data emerges from ongoing trials, the medical fraternity is inching closer to a paradigm where LSD is not seen through the lens of the past but as a potential harbinger of hope for individuals grappling with anxiety disorders. The quest for alternatives in mental health care propels the scientific inquiry forward, and LSD, with its psychedelic allure and emerging evidence of therapeutic utility, seems to be a part of this unfolding narrative.
As research continues and results are published, LSD will be seen as more than a party drug or something from a bygone era. Instead, clinicians around the globe are proving that LSD has a real place in the future of mental health and psychiatric care.
Sources
1. Holze, F., Gasser, P., Müller, F., Dolder, P. C., & Liechti, M. E. (2022). Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness A randomized, double-blind, placebo-controlled Phase II study. Biological Psychiatry, 93(3). https://pubmed.ncbi.nlm.nih.gov/36266118/
2. Inserra, A., Piot, A., Danilo De Gregorio, & Gobbi, G. (2023). Lysergic Acid Diethylamide (LSD) for the Treatment of Anxiety Disorders: Preclinical and Clinical Evidence. CNS Drugs, 37(9), 733–754. https://doi.org/10.1007/s40263-023-01008-5
3. Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease, 202(7), 513–520. https://doi.org/10.1097/nmd.0000000000000113
4. De Gregorio, D., Inserra, A., Enns, J. P., Markopoulos, A., Pileggi, M., El Rahimy, Y., Lopez-Canul, M., Comai, S., & Gobbi, G. (2022). Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits, and serotonergic neurotransmission decline. Neuropsychopharmacology. https://doi.org/10.1038/s41386-022-01301-9
5. Fuentes, J. J., Fonseca, F., Elices, M., Farré, M., & Torrens, M. (2020). Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials. Frontiers in Psychiatry, 10(943). https://doi.org/10.3389/fpsyt.2019.00943
6. Dolder, P. C., Schmid, Y., Müller, F., Borgwardt, S., & Liechti, M. E. (2016). LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality. Neuropsychopharmacology, 41(11), 2638–2646. https://doi.org/10.1038/npp.2016.82
7. Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Soltanzadeh Zarandi, S., Sood, A., Paddy, M. R., Duim, W. C., Dennis, M. Y., McAllister, A. K., Ori-McKenney, K. M., Gray, J. A., & Olson, D. E. (2018). Psychedelics Promote Structural and Functional Neural Plasticity. Cell Reports, 23(11), 3170–3182. https://doi.org/10.1016/j.celrep.2018.05.022
8. de Vos Cato M. H., Mason Natasha L., Kuypers Kim P. C. Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics, Frontiers in Psychiatry. Vol. 12, 2021. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.724606. DOI=10.3389/fpsyt.2021.724606. ISSN=1664-0640
9. Letheby, C., & Gerrans, P. (2017). Self unbound: ego dissolution in psychedelic experience. Neuroscience of Consciousness, 2017(1). https://doi.org/10.1093/nc/nix016
10. Simonsson, O., Stenfors, C. U. D., Goldberg, S. B., Hendricks, P. S., & Osika, W. (2023). Altered states of leadership: mindfulness meditation, psychedelic use, and leadership development. Frontiers in Psychology, 14, 1151626. https://doi.org/10.3389/fpsyg.2023.1151626
11. Less fear: How LSD affects the brain. (n.d.). ScienceDaily. https://www.sciencedaily.com/releases/2017/04/170404124640.htm
12. CTG Labs – NCBI. (n.d.). Clinicaltrials.gov. Retrieved October 24, 2023, from https://clinicaltrials.gov/study/NCT03153579?cond=Anxiety&term=LSD&rank=1
13. CTG Labs – NCBI. (n.d.). Clinicaltrials.gov. Retrieved October 24, 2023, from https://clinicaltrials.gov/study/NCT05407064
14. CTG Labs – NCBI. (n.d.). Clinicaltrials.gov. Retrieved October 24, 2023, from https://clinicaltrials.gov/study/NCT05883540?cond=Anxiety&term=LSD&rank=3
This material is not intended as a replacement or substitute for any legal or medical advice. Always consult a medical professional about your health needs. Psychedelics are widely illegal in the United States, and readers should always be informed about local, state, and federal regulations regarding psychedelics or other drugs.
Jason Najum