Psychedelic Assisted Psychotherapy and Sleep

Sleep may be important in the effectiveness of psychedelic psychotherapy.

Posted Dec 27, 2020

The Universe Within
Source: by Triff Standard License Royalty-free stock photo ID: 1059981530

As we near the end of a challenging year, I have been thinking about the tools we have to address psychological suffering. Psychological difficulties always exist but years with pandemics and wars have even greater stress and more anxiety, depression, and insomnia. There have been worse years than 2020, such as 1918 with both World War I and the influenza pandemic or 1945 with the Holocaust and atomic bomb. Still, 2020 stands out with so many things going wrong. Examples include massive wildfires worsened by climate change, demonstrations against systemic racism, and a pandemic that reached every continent. The demand for mental health services has stretched providers thin even as they cope with the pandemic themselves.

The search for more effective treatments for psychological disorders has continued. New therapies and medications have been developed. Recent psychiatric medications, however, are no more clinically effective than the medications developed decades ago. They have different and more benign side effect protocols than earlier medications but do not generally achieve significantly better results. New psychotherapies are promising but it is difficult to show greater effectiveness than older therapies.

As a result, there has been a reassessment of the clinical potential of the hallucinogens. There is evidence of use since prehistoric times and from the 1950s into the 1970s, these drugs were extensively researched for clinical use. Clinical research was stopped by the backlash against the use of these substances by the counterculture of the 1960s. 

Scientific studies resumed in 1990. Most research has been done on the psychedelics (primarily psilocybin), the dissociative anesthetics (ketamine), and the entactogens (MDMA). Ketamine is used as a standalone pharmacotherapy or with psychotherapy, while the psychedelics and entactogens are used to assist psychotherapy. All of these substances occasion experiences that have strong phenomenological similarity to the dream state. 

The serotonergic psychedelics, such as psilocybin, have powerful effects on perception, mood, and cognition while being physiologically safe with low dependency liability (Froese et al, 2018). They can, however, be very challenging psychologically and therapeutic benefit is best achieved with psychologically competent support.

A recent literature review (Breeksema et al, 2020) found that these substances have been examined for the therapeutic potential for a wide range of disorders including anxiety, depression, PTSD, and substance abuse. There are, for example, studies at Yale currently investigating the use of psilocybin in the treatment of OCD, body dysmorphic disorder, major depression, and several types of headache. (I am a therapist for one of these studies and information about them can be found here.)

Within a psychotherapeutic setting, these medicines affect insight and self-perception, cause feelings of connectedness, and occasion transcendent experiences and expanded emotional states. These contribute to symptom relief, increased self-awareness, and improved mood and quality of life. While promising, more research will be needed before it can be definitively proven that psychedelic therapy offers more rapid, powerful, and lasting benefits than current treatments. 

Froese et al (2018) argued that these substances may interact with sleep in ways that produce therapeutic benefits. In work with neural networks, it has been found that intermittently setting activity to random states leads to structural reorganization so that more effective neural coordination is facilitated by allowing the system greater space to explore. Likewise, sleep releases the nervous system from its normal constraints, which may facilitate learning and memory. Release from constraints is a characteristic of the psychedelic state and may allow the brain greater room to explore and thus improve its capacity for neural coordination. Froese et al (2018) suggested that psychedelics may interact with sleep and potentiate its effect of shifting the brain into non-ordinary spaces. This could increase the self-optimization effect of sleep.  

Some theories of psychological disorders suggest that they are caused by overly constrained mental processes that result in ruminative, critical thinking as seen in depression or in rigid patterns of thought in OCD. Other theories suggest that psychological disorders may result from a lack of effective organization of thought. 

Sleep is frequently disrupted by stress and sleep problems are a common symptom of psychiatric disorders. In health, sleep may function to reduce the neural activity of the waking brain that would, in time, become overly active and result in the inability to function effectively. Sleep may be important for psychological health because it helps reset the brain and facilitates more optimal organization or it may help to reduce neural activity and protect against overactivity and decreased function. Which of these is most important is unknown but two possibilities exist for how sleep interacts with psychedelic states to affect these patterns. 

There are many similarities between psychedelic and dream states as they involve similar experiences and have similar EEG patterns. The psychedelic state is, however, different in that it occurs in an activated, alert state unlike the deactivated state of sleep. If sleep functions to restrict plasticity then the disinhibiting effects of psychedelics would open the possibility of new learning and escape from constricted thought patterns. It is also possible that psychedelics counteract the effect of sleep deprivation and increase brain organization following the experience. Froese et al (2018) have analyzed data from animal studies that appear to show improvement in memory in a learning task following administration of psilocin, the active metabolite of psilocybin.

Ketamine is an FDA approved treatment for depression and can have significant psychedelic effects. It is a remarkably useful drug and is used for anesthesia and pain control and more recently as a treatment for depression (Gao et al, 2016). Studies are investigating how it has such a rapid therapeutic effect on depression (Tiger et al, 2020). Characteristic changes in the EEG of sheep given ketamine have been observed (Nicol & Morton, 2020) and a high dose caused a period of complete cessation of cortical EEG. The cessation of cortical EEG activity may explain the “k-hole,” which ketamine users often seek out. Ketamine significantly changes brain EEG and it is not unreasonable to suspect that this may have some implications for sleep. 

Several studies have shown that ketamine significantly affects sleep. A study by Feinberg & Campbell (1993) showed intensified NREM sleep in rats treated with ketamine. Ahnaou et al (2017) showed that, in rats, acute administration of ketamine has a different effect on sleep than chronic use. Abuse of ketamine is associated with poor sleep (Yen et al, 2020). Ketamine used in a medically safe environment is quite different from the sub-optimal conditions of illicit settings where dose and purity are questionable. The differential effects of acute versus chronic ketamine use must be considered in research with humans in order to determine the most effective dosing schedule.

Psychedelic drugs have a potentially important place in the treatment of many clinical disorders.  In the case of ketamine, approved treatments are already in use and FDA approval of MDMA and psilocybin appears increasingly likely in the near future. Much is to be learned about how psychedelics help bring about therapeutic change. Their interactions with sleep and its mechanisms will likely be an important part of the story.  


Ahnaou, A., Huysmans, H., Biermans, R., Manyakov, NV, & Drinkenburg, WHIM. (2017). Ketamine: differential neurophysiological dynamics in functional networks in the rat brain. Translational Psychiatry, 7(e1237); doi:10.1038/tp.2017.198 

Breeksema, J.J., Niemeijer, A.R., Krediet, E., Vermetten, E., Schoevers, R.A. (2020). Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies, CNS Drugs 34, p. 925–946; 

Feinberg, I. & Campbell, M.S. (1993). Ketamine administration during waking increases delta EED intensity in rat sleep. Neuropsychopharmacology9(1), p. 41- 48.

Froese, T., Leenen, L., & Palenicek, T. (2018). A role for enhanced functions of sleep in psychedelic therapy? Adaptive Behavior26(3);

Gao, M., Rejaei, D. & Liu, H. (2016). Ketamine use in current clinical practice. Acta Pharmacologica Sinica, 37, 865–872

Nicol, A.U., & Morton, A.J. (2020). Characteristic patterns of EEG oscillations in sheep (Ovis aries) induced by ketamine may explain the psychotropic effects seen in humans. Scientific Reports10, 9440;

Tiger, M., Veldman, E.R., Ekman, C-J, Halldin, C., Svenningsson, P., & Lundberg, J. (2020). A randomized placebo-controlled PET study of ketamine’s effect on serotonin 1B receptor binding in patients with SSRI-resistant depression, Translational Psychiatry10(159);

Yen, CF., Lin, HC., Ko, CH., Wu, HC., Hsu, CY., Wang, PW. (2020). Sleep quality among individuals with ketamine use and the mediating role of craving. Scientific Reports10, 20535