Importance Of Psychedelics

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Psychedelic drugs have profound effects on the brain, substantially altering perception, mood, and even the hardwiring of our brains.

Because of their potential to cause a long-term changes to how our brains process information and emotions, drugs like MDMA, LSD, and psilocybin are being studied as a possible breakthrough for mental health treatments. While studies on the clinical use of psychedelics are showing great promise, one big question remains: Is the psychedelic experience necessary to gain the mental health benefits?

Minding memory

While Hutson — who has a breadth of experience studying psilocybin and MDMA — handled the design of the participants’ medicated experience, Wenthur set up the protocols for testing the effectiveness of the combination on elimination of memory traces.

The vial in which the psilocybin capsules are delivered to the School of Pharmacy for clinical research.

To understand whether memories for particular facets of the experience are more relevant than others, Wenthur will be quantitatively assessing amnesia for various domains of stimuli and the persistence ...
... and fidelity of these reports across time. The study team will be assessing multiple domains because they hypothesize that not all memories are likely to be equivalently relevant to the potential therapeutic effects of psychedelic-assisted psychotherapy. These memory tests will incorporate well-established analytical approaches across both known tasks and some more novel, exploratory approaches.

Through this study, as well as additional efforts in animal models, Wenthur hopes to shed light on how different signaling pathways intersect with one another to influence neuroplastic outcomes. Hence, the combination of the psilocybin and midazolam could be affecting memory as well as the signaling that’s actually occurring in the brain.

A powerful, collaborative approach

Hutson and Wenthur both have a breadth of expertise in research regarding new therapeutics for psychiatric disorders, including treating opioid use disorder with psilocybin, PTSD with MDMA, and major depression with ketamine.

The pair are also some of the main forces behind the creation of a new, first-of-its-kind, master’s degree option in Psychoactive Pharmaceutical Investigation at the School of Pharmacy, with the first class now enrolling for fall 2021.

In addition to Wenthur and Hutson, the research team is composed of a diverse group of investigators from across the UW–Madison campus, including Christopher Nicholas and Randall Brown of the Department of Family Medicine and Community Health, Chuck Raison of the School of Human Ecology, John Dunne of the Center for Healthy Minds, and Richard Lennertz and Matthew Banks of the Department of Anesthesiology.

“This study and its research team exemplifies the transdisciplinary nature of research with psychedelic drugs such as psilocybin,” says Hutson.

For this pilot study, slated to begin in May 2021, the research team is first hoping to confirm that the combination is safe and effective in producing a psychedelic experience that patients don’t remember, laying the groundwork for a future study of its impact on adults with major depressive disorder.

A Connection to General Health?

It’s important to remember that correlation does not establish causation. In this context, psychedelic users being more physically healthy does not necessarily suggest that psychedelics were the direct cause of the improvement. It could be that those who are more health-conscious would be more likely to stumble upon and try psychedelics. Similarly, recent research indicates that the insights people gain from psychedelics may lead them to adopt a healthier lifestyle. 

The mind and body exist in a closed circuit. All illness is going to involve physical symptoms that manifest in our consciousness. Treatments at the physical level have effects at the psychological level, and vice versa. 

Having said that, a growing number of studies point to the effectiveness of psychedelics in treating various physical ailments that people do not usually associate with the psychological, such as headaches. 

Psychedelics Treating Inflammatory Conditions

Inflammation is the body’s natural mechanism to protect us from harm. The process involves increased blood flow, proteins, and antibodies to the area of injury. Although the inflammatory response is critical to survival during injury, research has revealed that certain lifestyle factors including smoking, obesity, and chronic stress can lead to chronic inflammation (CI) which in turn can result in a wide array of serious diseases including cancer, cardiovascular disease, and autoimmune and neurodegenerative disorders. 

For that reason, it is particularly exciting that researchers have discovered evidence that psychedelics have potent anti-inflammatory properties. In fact, certain drugs targeting 5HT2A receptors (as psychedelics do) seem effective in treating a wide range of inflammatory conditions in rats, including asthma and coronary artery disease.

In addition, researchers have completed phase 1 clinical trials on psychedelics to treat Alzheimer’s and other neurodegenerative diseases using LSD, thanks to its anti-inflammatory properties. The study demonstrated the safety and tolerability of 5-20 μg LSD in older healthy individuals.

Building upon these findings, researchers, in conjunction with the life sciences company Eleusis, are developing new drugs that act on the 5HT2A receptor to treat inflammatory conditions, yet which do not affect behavior. These findings stand to help treat a wide array of physical ailments associated with inflammation.

Psychedelics and Migraine Headaches

According to the Migraine Research Foundation, migraines are the third most prevalent and sixth most disabling illness in the world, affecting 12% of the population. Over 90% of sufferers are unable to work or function normally during a migraine. Researchers estimate the annual lost productivity costs of migraines in the U.S. at around $36 billion.

For years, anecdotal evidence has suggested that psychedelics can be effective in treating migraines. The first ever clinical trial to study psychedelics for migraines emerged earlier this year. Researchers from the Yale School of Medicine administered a low dose of psilocybin to 10 patients suffering from frequent migraines.  

Those who took psilocybin experienced a significant reduction in the frequency of migraines over a 2-week period. Furthermore, psilocybin users had significantly reduced migraine-induced pain and functional impairments. 

Psychedelics and Cluster Headaches

Cluster headaches (CH) can be some of the most painful experiences possible. Patients experience cluster periods, generally lasting between weeks and months, during which headaches usually occur every day or even multiple times a day. Each attack typically lasts between 15 minutes and 3 hours. Unsurprisingly, CH patients very often experience chronic depression, anxiety, and PTSD. The causes of CH remain largely unknown and there is no cure.

Like migraines, anecdotal evidence of the efficacy of psychedelics to treat CH drove initial research. In 2006, researchers published a study in which they surveyed 53 patients about their use of psychedelics to treat their CH. The results were overwhelmingly positive. 85% of patients found psilocybin effective in aborting attacks. 88% of patients found LCD effective in terminating their CH episode. Finally, LCD and psilocybin were very effective at extending patients’ remission periods (80% and 91% respectively). 

No other preventative medication has achieved results as positive. Quoting a qualitative study, CH patients who use LSD “often experience full remission… and can potentially CURE cluster headaches!” Subsequently, Yale University is close to completing the first ever controlled clinical trial to validate these findings. 

How do Psychedelics Treat Headache Disorders?

Both CH and migraine are headache disorders, or neurological conditions characterized by recurrent attacks. They do not seem to be rooted in the psychological realm. Yet psychedelics present great promise in providing effective treatment for these debilitating illnesses. 

The causes of headache disorders are not wholly understood. Studies such as this one have identified multiple brain regions to be involved in producing and maintaining headache attacks. It is therefore unsurprising that the mechanism of action of psychedelics to treat headache disorders is not totally clear either. However, in a lecture on headache disorders given at the recent PsyTech summit, Dr. Emmanuelle Schindler from the Yale School of Medicine suggested the following as areas worth exploring: hypothalamic and hormonal function, inflammatory systems, and circadian rhythms.

Importantly, we need further research to confirm these initial findings – research with larger and more representative sample sizes, longer durations of observation, and more experimentation with different dosages and frequencies of use. 

To Conclude

There is a plenitude of areas of disease that are worth mentioning here yet as of yet, many lack clinical or animal trials. These include autoimmune conditions, brain injury, and phantom limb pain, among others. 

A great deal more research is needed to fully understand the magic of how psychedelics treat both the symptoms and causes of such a wide array of diseases. But what does seem clear is that the benefits of psychedelics for mental health are likely to be just the tip of the iceberg.

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