The BioPharmaceutical Technology Center Institute, which is located at Promega Corporation in Madison, Wisconsin, recently hosted the 10th Annual International Bioethics Forum titled “Manifesting the Mind”. Several notable speakers gave presentations on a rather unexpected subject matter: the use of hallucinogens such as psilocybin (i.e., magic mushrooms) to better understand the nature of consciousness and to even treat neuropsychological disorders such as depression, anxiety and drug addiction. I was one of the lucky participants that attended this forum.

Unlike scientism, science in the true sense of the word is open to unbiased investigation of any existing phenomena.
-Stanislav Grof

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), which is the active ingredient in psychedelic mushrooms, has been in use for thousands of years by the indigenous peoples of the Americas; in fact, the Aztec called these mushrooms teonanacatl, or “flesh of the gods”. Mescaline (the psychoactive ingredient in peyote cactus) is another type of hallucinogen that was widely used by the Native Americans living in what are now parts of Southwest America and Mexico; even today the peyote cactus figures prominently in religious rituals celebrated by the Navajo and other Indian tribes. LSD (d-lysergic acid diethylamide), another type of hallucinogen, was more recently discovered by Dr. Albert Hofmann in 1943 and then popularized by the “counterculture” movement of the 1960s.

The study of hallucinogens and their mode of action on the brain have been conducted since the late 1800s (1). By the 1960s, studies of hallucinogens and their effects on consciousness had accelerated dramatically (2–4). Unfortunately, due in part to the antics of drug enthusiasts such as Dr. Timothy Leary, public and scientific interest in and support of hallucinogen research essentially stopped. It was not until the mid to late 1990s, when better study controls could be implemented, that researchers resumed their investigation of hallucinogenic substances and the effects of these agents on the mind and body.

Nowadays, researchers and doctors have renewed their interest in psychedelic substances such as psilocybin because these substances have been found to be effective in the treatment of several challenging behavioral and mental issues like repressed memories (5), alcohol, tobacco and narcotic drug addiction (6), headaches (7) and depression as a result of advanced and/or terminal cancer (8, 9). After first prescreening potential study candidates for mental stability and no prior hallucinogen use, these researchers and doctors administer controlled amounts of the hallucinogenic drug psilocybin. Study participant reactions are then meticulously logged and charted. In many cases, functional MRI (fMRI) and/or PET scans are administered during the psychedelic experience in order to evaluate brain activity. Some rather intriguing results have already been collected from these studies, including the following 10 surprise findings:

1. Lack of addiction. Narcotic drugs like cocaine prevent the reuptake of pleasure/learning-associated neurotransmitters such as dopamine, eventually leading to addiction due to the strong reward feedback loop that narcotics create. Alternately, the hallucinogen psilocybin acts as an agonist (activator) of the 5-hydroxytryptamine (5-HT) receptors 5-HT1A, 5-HT2A and 5-HT2C, much like the natural 5-HT receptor agonist serotonin.  Serotonin, unlike dopamine, is associated more with general well-being and memory and less so with short-term pleasure, a key difference that is thought to remove it from the addiction pathway.

2. Anxiety reduction. Dr. Stephen Ross has studied psilocybin-assisted psychotherapy as a treatment method for patients who are suffering from feelings of anxiety and depression as a result of being diagnosed with advanced/terminal cancer. The findings of the NYU Psilocybin Cancer Project, of which he is the principal investigator, indicate that patients with advanced/terminal cancer benefit from the administration of psilocybin in terms of their spiritual and mental well-being and reduced levels of anxiety, depression and pain. This is not surprising in light of the discoveries made by Dr. Franz X. Vollenweider, who has found that psilocybin reduces prefrontal cortex control over the amygdala, the so-called fear center of the brain. Incidentally, Dr. Vollenweider has also published reports on the reduction of depression in patients who regularly partake of psilocybin.

3. Quantum behavioral change. Society’s overall perception of individuals who partake in psychedelic substances is that they are anti-social and anti-establishment “misfits”, “burnouts” and “dope heads”. However, research that is being conducted by Dr. Roland Griffiths at the Johns Hopkins University indicates that taking psilocybin can produce positive changes in the personality, attitudes and behavior of participants (10). Individuals who have taken psilocybin report having renewed or stronger feelings of societal responsibility, empathy towards others and a fundamental understanding of the interconnection between all living things. The perceptual and cognitive changes incurred during the psilocybin encounter are partly to credit for these quantum behavioral changes.

4. Mystical-type experience.  The Institute of Noetic Sciences, of which Dr. Roland Griffiths is a part, is actively studying the mystical experiences that are encountered by study participants who take psilocybin or other hallucinogens. In many cases, neuronal responses and brain wave patterns of individuals who are administered psilocybin are akin to those measured during states of fasting, prayer, meditation or other religious/spiritual ecstasy (11). There is also a planned collaborative study between Drs. Roland Griffiths and Richard Davidson (University of Wisconsin-Madison) to find out if hallucinogens can aid individuals who are regular and experienced practitioners of meditation in terms of their overall focus, session length, and spiritual progress. The participants of this study will be screened at Johns Hopkins University and then tested via fMRI at the University of Wisconsin-Madison.

5. Cigarette smoking cessation. Ongoing pilot studies at Johns Hopkins University with psilocybin have suggested that this hallucinogen may actually help individuals overcome their nicotine addiction (6, 12). Thus far, of the 3 volunteers tested, 1 has been in nicotine remission for at least 6 months while the other 2 have been in remission for over 12 months. Current research is focused on finding the mechanism behind hallucinogen treatment of nicotine as well as other drug addictions.

6. Deep personal significance. Individuals who have taken psilocybin reported that the experience was one of the five most significant events in their lives. This opinion continued even 14 months after the psilocybin experience (13), arguing that the so-called psychedelic “trip” is not something to be taken lightly or dismissed.

7. Neuroplasticity. Neuroplasticity is defined as neuronal change that typically occurs in response to a stimulus, be it a hormone, environmental cue or behavior. In the case of psilocybin, repeated exposure of the brain to this substance may induce neuroplasticity via the modulation of discrete neural circuits. The work of Dr. Franz X. Vollenweider of the Heffter Research Institute has suggested that psilocybin influences glutamate release in the prefrontal cortex. Glutamate activates BDNF (brain-derived neurotrophic factor), a nerve growth factor that is key to neural growth, development and survival (14). The psychological changes that have been found to occur in individuals who take psilocybin, such as reduced levels of depression, can be attributed to heightened glutamate.

8. Obsessive-compulsive disorder treatment. Dr. Francisco A. Moreno of the University of Arizona is exploring the treatment of obsessive-compulsive disorder, or OCD, with psilocybin (15). Preliminary results look promising, with some patients remaining symptom-free for days following the treatment. One patient remained symptom free for almost 6 months. No other treatment has thus far been found to alleviate OCD symptoms as quickly as psilocybin.

9. Cluster headache treatment. A cluster headache is a headache of unusually high intensity that lasts anywhere from 15 minutes to 3 or more hours. Cluster headaches will recur on a periodic basis but may also undergo occasional spontaneous remission. Both psilocybin and LSD have been shown to prevent the incidence of or to treat cluster headaches with amazing success (7).

10. Repressed memory recall. In some cases, the ingestion of psilocybin has allowed certain individuals to recall suppressed emotional memories. The Beckley Foundation, in collaboration with fMRI expert Dr. Karl Friston, will be studying subjects who have ingested psilocybin to determine if and how psilocybin allows suppressed memories to surface (5).

Of course, not all is rosy when it comes to hallucinogens. Roland Griffiths reported that, even under careful supervision by study coordinators, individuals who took psilocybin did sometimes experience fear and anxiety during the experience. Roughly 1/3 of the volunteers had feelings of fear and anxiety when administered high (30mg/70kg) doses of psilocybin. Another 9% of participants reported that their entire session was dominated by anxiety, while 26% had mild and transient paranoid thinking.

There is also very little information about the long-term side effects of psilocybin use. Short-term side effects, such as addiction or neurotoxicity/excitotoxicity, do not appear to be at issue; however, there is no certainty that serotonin receptor down-regulation (i.e., hallucinogen tolerance), by-product buildup and possible sequestering or neurodegenerative disease do not appear after prolonged use of hallucinogens.  Such side effects may require decades of time before they became evident, and therefore would not be reported in human research trials performed only 15-20 years ago.

While not all questions have been answered about psilocybin and other hallucinogens, there is a plethora of evidence suggesting that they may have therapeutic potential for various mental and behavioral issues. Likewise, these so-called psychedelics may also become a unique window into humanity’s soul.

References:

1. Mitchell SW. Remarks on the effects of Anhelonium lewinii (the mescal button). The British Medical Journal. Dec 5 1896, 1625–9.
2. Huxley, Aldous. Drugs that Shape Men’s Minds.
3. Cohen, S. (1960) Lysergic acid diethylamide: Side effects and complications. J. Nerv. Ment. Dis. 130, 30–40.
4. Unger, S. M. (1963) Mescaline, LSD, Psilocybin and Personality Change. Psychiatry: Journal for the Study of Interpersonal Processes. 26, May 1963.
5. Psilocybin and Memory. The Beckley Foundation
6. Psilocybin-Facilitated Treatment of Addiction – A Beckley Foundation/Johns Hopkins Collaboration
7. Sewell, R.A., Halpern, J.H. and Pope, H.G. Jr. (2006) Response of cluster headache to psilocybin and LSD. Neurology 27 1920–22.
8. Hallucinogens Have Doctors Tuning In Again https://www.nytimes.com/2010/04/12/science/12psychedelics.html
9. Grob, C.S. et al. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. Jan;68(1):71–8. Epub 2010 Sep 6.
10. Psilocybin and quantum change in attitude and behavior” with Roland Griffiths
11. Griffiths, R.R. et al. (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl). 187, 268–83; discussion 284-92. Epub 2006 Jul 7.
12. Psilocybin in Smoking Cessation: A Pilot Study. Horizons 2010: Psilocybin in Smoking Cessation: A Pilot Study – Matthew W. Johnson, Ph.D. and Mary P. Cosimano, MSW
13. Griffiths, R. et al. (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 22, 621–32. Epub 2008 Jul 1.
14. Finsterwald, C. et al .(2010) Regulation of Dendritic Development by BDNF Requires Activation of CRTC1 by Glutamate J. Biol. Chem. 285, 28587–95.
15. Francisco, A. et al. Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder J Clin Psychiatry 2006;67:1735-1740.