Psychedelic Medicines for Pain Go Mainstream

An estimated 32 million individuals 12 years and older used psychedelic medicine in the United States in 2010, according to a US population survey. As the opioid epidemic has eclipsed concerns about illegal drugs in recent years, the medical community and the federal government alike have begun reexamining certain illicit drugs as potential alternatives to opiates in pain management.

Cannabis

Perhaps no other "illicit" substance has played a greater role in turning the tides recently than medical cannabis. Its slow but steady serial legalization and decriminalization at the state levels to treat a variety of complaints, including pain, have helped bring cannabis, cannabis products, and other stigmatized drugs to the forefront.

"It is most surprising that even though cannabis has been used for a number of ailments for thousands of years—even dating back to the 28th century BC—it is now being recognized as a valid treatment option," said Swathi Varanasi, PharmD, an integrative health pharmacist and medical cannabis consultant in Los Angeles, California. "However, because of the way cannabis has been criminalized, it hasn't been integrated into standard treatment algorithms.'

Regulatory measures aside, pharmacists and other members of the medical profession often wrestle with safety when assisting patients who use cannabis for medicinal purposes. Cannabis has been studied extensively for numerous uses, including its potential benefits in neuropathic pain, chronic pain, and inflammation. A 2014 study found that most patients cited relief from chronic pain as the most common reason for their medicinal use of cannabis. Yet the plant's psychoactive properties continue to draw concerns regarding abuse potential, owing to the effects of 1 phytochemical, Delta-9-tetrahydrocannabinol, known for its psychoactive properties.

However, these are not the only challenges pharmacists face when it comes to assisting patients. "The biggest pitfall in advising patients on cannabis is that dosing is so difficult to standardize," Victoria Starr, RPh, a cannabis pharmacist at SageLife, LLC, in Portland, Oregon, told Drug Topics®.

Cannabis for medicinal purposes is highly complex, largely because of its high number of phytochemicals, called constituents. To date, the plant has been found to contain more than 560 constituents. When individuals consume these as the whole plant, the chemicals ofery synergistic and therapeutic benefits while mitigating potential toxicities, what's known as the entourage effect. Synthetic cannabis typically contains only 1 active ingredient and lacks additional chemicals that can help regulate undesirable effects. However, customizing cannabis dosing to even the individual patient is no small feat.

"Besides attaching medical benefits to each of these components, the combination of synergistic benefits needs to be determined, along with the proper ratio and dose," Starr explained. "So unlike Western medicine, in cannabis, there exists a multitude of different medications—with a wide range of potencies, targeting a vast array of medical conditions—made up of varied combinations of cannabinoids, terpenes, and flavonoids.

Psilocybin

Psilocybin, the primary ingredient found in mushrooms that produce psychoactive effects, in enjoying an increased share of popularity and renewed exploratory use.

It’s exciting that patients are starting to ask their pharmacist about psilocybin,” said Emily Kulpa, PharmD, an integrative health pharmacist and psychedelic medicine consultant based in Milwaukee, Wisconsin.

Although psychedelic mushrooms have been used for millennia, they gained popularity in the United States for recreational use during the 1960s and had spawned some academic interests as well. From 1960 to 1962, psilocybin, along with psychedelic relatives lysergic acid diethylamide (LSD) and mescaline, became the focus of a series of trials known as the Harvard Psilocybin Project. At the time, these drugs were legal. Criminalization of these drugs would later erupt in the following decade as safety concerns grew.

Fast-forward to the new millennium. Psilocybin sparked some interest in its potential analgesic effects in cluster headaches and migraines. Psilocybin agonizes the 5-hydroxytryptamine receptor and may interact with nociceptive and antinociceptive processing. The results from one 2016 retrospective study Googling the keywords “cluster headache discussion forums” and “migraine discussion forums” found that patients who self-treated themselves with psychedelic tryptamines such as psilocybin and LSD reportedly experienced a reduction in cluster frequency and severity.

Although these claims may warrant clinical study in pain management, research has focused on the role of psilocybin in mood disorders. Kulpa credits events in popular culturwith helping bring psilocybin into the mainstream. In the fall of 2019, Johns Hopkins announced the opening of the Center for Psychedelic & Consciousness Research, the first institution in the United States devoted exclusively to psychedelic research.

Kratom

Indigenous to Thailand, Malaysia, Myanmar, and other regions of Southeast Asia, kratom (Mitragyna speciosa) belongs to the coffee family and also exhibits dose-dependent sedative and stimulatory effects. The plant is typically consumed in pill, capsular, or extract form, although some individuals brew dried or powdered leaves as a tea. Others may chew, smoke, or consume the leaves in food. However, because of kratom’s harmful adverse effects and abuse potential, the FDA warns individuals against using the substance.

Kratom contains mitragynine, an alkaloid bearing a tryptaminelike structure that exhibits µ- and ∂-opioid receptor agonist activity that results in dose-dependent stimulatory and analgesic effects. In lower doses, mitragynine produces stimulatory effects, whereas higher doses result in opioid-like activity. However, its metabolite, 7-α-hydroxymitragynine, exhibits significantly stronger µ-opioid receptor agonist behavior.

Although kratom is not an opioid, the CDC found an association between kratom use and overdose deaths, also involving opioid and nonopioid use, in the State Unintentional Drug Overdose Reporting System. Moreover, based on toxicology results, medical examiners or coroners determined kratom as the culprit in deaths in 11 states from July 2016 to June 2017 and 27 states during the last 6 months of 2017.

“There is no legitimate medical use for kratom in the [United States],” the Drug Enforcement Administration (DEA) wrote in a report on its website.8 On August 16, 2016, the DEA announced its intent to classify kratom as a Schedule I controlled substance, noting that the plant had been “abused for its ability to produce opioidlike effects” and “was often marketed as a legal alternative to controlled substances.”

Pharmacists should be aware of the substance so they can educate patients about the potential harms.

Psychedelic Medicine in the Near Future

Varanasi believes the importance of cannabis in pain management will only continue to grow. “Preliminary evidence demonstrates cannabis’ ability to provide significant pain relief as well as [to help individuals] taper off opioids [particularly in the setting of addiction],” she said. “Though the research is inconclusive, patient anecdotes support the continued use of cannabis in pain management.”

In Oregon, the Oregon Psilocybin Program Initiative will appear on ballots in November 2020. “If passed, it would [be] the first state-sanctioned program for the administration of psilocybin services between a certified practitioner and a patient,” Varanasi said. “This would not only set the standard for other states but also support published studies reporting that a strong patient-practitioner relationship improves overall health outcomes.”

In the meantime, patients and practitioners alike will have wait to see how these and other psychedelics will alter integrative medicine and the world of health care.

References

1. Krebs TS, Johansen P-Ø. Over 30 million psychedelic users in the United States. F1000RED. Preprint posted online March 28, 2013. doi:10.12688/F1000research.2-98.v1
2. Light MK, Orens A, Lewandowski B, Pickton T. Market size and demand for marijuana in Colorado. The Marijuana Policy Group. 2014 [November 17, 2016]
3. ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of cannabis sativa L. Prog Chem Org Nat Prod. 2017;103:1-36. doi:10.1007/978-3-319-45541-9_1
4. Doyle J. Legend of a mind: Timothy Leary & LSD. November 26, 2014. Updated March 20, 2020. Accessed June 1, 2020. https://www.pophistorydig.com/topics/tag/psychedelic-drugs-1960s/
5. Whelan A, Johnson MI. Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role? Pain Manag. 2018;8(3):217-229. doi:10.2217/pmt-2017-0068
6. Andersson M, Persson M, Kjellgren A. psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduct J. 2017;14(1):60. doi:10.1186/s12954-017-0186-6
7. About. Johns Hopkins Center for Psychedelic & Consciousness Research. Accessed June 1, 2020. https://hopkinspsychedelic.org
8. KRATOM (Mitragyna speciosa korth). Drug Enforcement Administration. November 2019. https://www.deadiversion.usdoj.gov/drug_chem_info/kratom.pdf.
9. What is kratom? National Institute on Drug Abuse. April 2019. https://www.drugabuse.gov/publications/drugfacts/kratom
10. FDA and Kratom. FDA. Updated September 11, 2019. Accessed June 4, 2020. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom
11. Olsen EO, O’Donnell J, Mattson CL, Schier JG, Wilson N. Notes from the field: unintentional drug overdose deaths with kratom detected — 27 states, July 2016–December 2017. MMWR Morb Mortal Wkly Rep. 2019;68(14):326-327. doi:10.15585/mmwr.mm6814a2
12. Kruegel AC, Uprety R, Grinnell SG, et al. 7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. ACS Cent Sci. 2019;5(6):992-1001. doi:10.1021/acscentsci.9b00141
13. DEA announces intent to schedule kratom. News release. Drug Enforcement Administration. August 30, 2016. https://www.dea.gov/press-releases/2016/08/30/dea-announces-intent-schedule-kratom