Non-Psychoactive Benefits of Psychedelics

By Christopher Gunlock

Image released under Creative Commons CC0/Public Domain

  Evidence is building that paints a picture of physically measurable changes that don’t require the numerous psychoactive effects of popular psychedelics. As one would expect, the brain has been the featured human structure in these studies, so we can begin this investigation by looking at a potential psychedelic treatment for a particularly rare condition known as cluster-headaches (CH).

             Cluster-headaches (CH) are similar in most ways to migraines except for how certain symptoms manifest. Migraines accompany multiple bodily discomforts that last in varying intensities for several hours. CH hits a more localized spot in the head for shorter, reoccurring periods. Other than that, both are thought to be associated with a few specific genetic pathways, biochemical pathways, hormonal changes, and medications [1].

             While less common than migraines, CHs are near-unbearable for those that can’t find relief from conventional interventions [1], [2]. Sadly, some even refer to CHs as “suicide headaches.” On the bright side, this creates a prime opportunity for bold researchers to gain access to the heavily-restricted, but valued treasure of psychedelics.

             Fortunately for researchers, the results of CH treatment were distinguished. The benefits to CH were as good or better than conventional treatments in clinical tests, and a lasting remission after a single dose was more common with both lysergic acid diethylamide (LSD) and N, N-dimethyltryptamine (DMT) than any other treatment. Both the acute treatment of sudden attacks and preventative dosing have been reported to be effective [3]. Psilocybin treatment for CH has had similar results [4].



             Sub-perceptual doses, which give rise to non-psychoactive experiences, have even been found to be effective [3]. This connection to CHs has been known for some time, and as one would expect, researchers collecting online reports found a number of afflicted patients choose to seek out controlled substances as an alternative [5]. Despite this risky behavior of using illicit substances unsupervised, for some it has occasionally paid off, as one recent survey study describes [6].



             Outside of this breakthrough research, conventional treatment offers a variety of acute and preventative interventions. Acute treatment would be something the sufferer has on hand that aims to stop a headache as it starts. For example, oxygen, various pharmaceutical nasal sprays, and anti-inflammatories offer some relief, but harmful side effects and lack of long-term reliability cries out for new options [1].

             Preventative, daily doses of anti-inflammatories, vasodilators, blood flow restrictors, electrical stimulation, and aspirin have a beneficial effect, but the reasons many can’t rely on them are similar to the risks and reliability issues of acute treatment [1], [2].

             Another recent finding in neurobiology suggests psychedelics may have distinct physical benefits in the brain. Discoveries of dendritic growth on both animal studies and isolated cell cultures point to the physical changes being independent from the psychoactive experience [7].  Dendrites are not only extensions of the neuron, but are the reason new connections to other neurons can be made. When these dendritic branches retract, we see illnesses like depression/anxiety and post-traumatic stress disorder (PTSD) appear [8].            

             Furthermore, these studies successfully showed changes in neuronal growth regardless of the sample being a vertebrate or invertebrate species, which implies that these psychedelics have a basic evolutionary function in neurons [7]. Therefore, when one considers both sub-perceptual dose efficacy and these recent neurological findings, the non-psychoactive effects appear to be independent of any psychoactive psychedelic experience.

             From one perspective, the psychedelic trip itself could be considered a side-effect of this new treatment. For example, one individual with CHs who appeared in a National Geographic documentary reported hating the psychoactive experience when he takes his psilocybin mushrooms every 2 months [9]. His distaste for the experience combined with the legal risks of using a highly restricted substance was still not enough to stop him from growing his own supply.

             Similarly, a qualitative analysis of self-submitted reports showed a large number of psychedelic users had little interest in the psychoactive effects in favor of the treatment of their CH [3]. However, if one considers the perceptual alterations as a way to other forms of healing, the headache sufferer may want to reconsider the severity of this “side effect.”

             While it is remarkable that psychedelics offer what looks like a more sustainable solution to CHs, there are bigger and further-reaching questions that arise.

  • Do psychedelics regrow your brain cells?

  • Are there neurological afflictions other than CHs and depression/anxiety where psychedelic neurogenesis can help?

             In fact, there are scientists answering these questions now, but perhaps if more of us start pondering them too, these pioneering scientists will be more likely to garner support being curious about such tightly controlled substances. 


[1]       M. Wilkinson, V. Pfaffenrath, J. Schoenen, H.-C. Diener, and T. Steiner, “Migraine and Cluster Headache-Their Management with Sumatriptan: A Critical Review of The Current Clinical Experience,” Cephalalgia, vol. 15, no. 5, pp. 337–357, Oct. 1995.

[2]       A. L. Vollesen et al., “Migraine and cluster headache – the common link,” J. Headache Pain, vol. 19, no. 1, p. 89, Dec. 2018.

[3]       M. Andersson, M. Persson, and A. Kjellgren, “Psychoactive substances as a last resort-a qualitative study of self-treatment of migraine and cluster headaches.,” Harm Reduct. J., vol. 14, no. 1, p. 60, Dec. 2017.

[4]       R. A. Sewell et al., “Response of cluster headache to psilocybin and LSD.,” Neurology, vol. 66, no. 12, pp. 1920–2, Jun. 2006.

[5]       C. Di Lorenzo, G. Coppola, G. Di Lorenzo, M. Bracaglia, P. Rossi, and F. Pierelli, “The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey,” Cephalalgia, vol. 36, no. 2, pp. 194–198, Feb. 2016.

[6]       E. A. D. Schindler, C. H. Gottschalk, M. J. Weil, R. E. Shapiro, D. A. Wright, and R. A. Sewell, “Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey,” J. Psychoactive Drugs, vol. 47, no. 5, pp. 372–381, Oct. 2015.

[7]       C. Ly et al., “Psychedelics Promote Structural and Functional Neural Plasticity.,” Cell Rep., vol. 23, no. 11, pp. 3170–3182, Jun. 2018.

[8]       M. Banasr, J. M. Dwyer, and R. S. Duman, “Cell atrophy and loss in depression: reversal by antidepressant treatment,” Curr. Opin. Cell Biol., vol. 23, no. 6, pp. 730–737, Dec. 2011.

[9]      Hewes, J. (Producer), (2012). Drugs Inc. Season 2 Episode 4: Hallucinogens. [Documentary]. United States: Wall to Wall Media Ltd.