Alan F. Schatzberg, MD

 

Madness Rising

Research into Hallucinogens Gives Hope to the Hopeless and Fuels a Drug Epidemic: A Tale of Two Disparate Worlds

By James M. La Rossa Jr.
Editorial Director and Publisher

 

In Robert Stone’s influential book about the heroin trade that permeated the Vietnam War, Dog Soldiers, Stone describes the decision by the U.S. Military Advisory Command in Vietnam to designate elephants as enemy combatants because the Viet Cong used the animals to transport materials. The U.S. then sent helicopter gunships throughout Vietnam to destroy the elephants with machine guns. Disgusted soldiers dubbed the action The Great Elephant Zap. Dog Soldiers main character analogizes the Elephant Zap to overcome his moral objection to smuggling heroin. “If the world is going to ‘contain’ elephants pursued by flying men, people are just naturally going to want to get high.” Since all of America was “getting high,” why not get in on the action?

Like our Vietnam War-era brethren, are we, too, in the grips of some sort of rising madness? Practical evidence seems to suggest we may be.

The question is, how wittingly? New research quantifying the psychiatric benefits of recreational drugs like MDMA, ketamine, LSD and psilocybin, especially in refractory patients, are clearly fueling the search to improve quality of life through drug experimentation.

How, though, do we square the contrast between the use of LSD, for example, to improve mood, and the opioid epidemic in full bloom throughout the Nation? Moreover, the use of potential drugs of abuse, such as opioids, to treat psychiatric disorders, seems to have favor with thought leaders over “experimental” treatments like ketamine infusions. (See Alan F. Schatzberg’s ingenious commentary, Opioids in Psychiatric Disorders: Back to the Future? http://October 24, 2017 www.medworksmedia.com From: Michael E. Thase, MD, Editor-in-Chief James M. La Rossa Jr., Editorial Director & Publisher(https://doi.org/10.1176/appi.ajp.2015.15101354)

Back to the Future seems to have suggested the existence of this very conundrum. Schatzberg, Yovell and colleagues (1) point to the potential use of low doses of a buprenorphine, a mu-opioid partial agonist, to decrease suicidal ideation in psychiatric patients.  The findings are in keeping with earlier work of Bodkin et al. (2), who found that buprenorphine could provide relief to patients with refractory depression, and the more recent work of Ehrich et al. (3), who found that buprenorphine in combination with a mu-opioid antagonist—samidorphan—may be effective in refractory major depression.

Do the legitimate use of opioids in psychiatry, in tandem with legal psychiatric research into another class of abuse — hallucinogens — give patients “license” to experiment with the burgeoning class of “illegals?” Like the protagonist in Stone’s Dog Soldiers, “In a world where physicians are ‘high’ on the uses of opioids and hallucinogens, everyone’s going to want to experiment.” Most importantly, how much of this “experiment” is responsible for the epidemic in opioid abuse?

Dedicated chat sites like reddit have, quite literally, tens of thousands of subscribers wanting to learn about microdosing LSD for mood enhancement (https://www.reddit.com/search?q=microdosing). Currently – legally – we’re in the midst of a psychedelic renaissance. New York University, the University of New Mexico, the University of Zurich, Johns Hopkins University, the University of Alabama and the University of California-Los Angeles have all partnered with the psilocybin-focused Heffter Research Institute, studying the compound for smoking cessation, alcoholism, terminal-cancer anxiety and cocaine dependence. Then there is the biotech-CEO-founded Usona Institute funds research of “consciousness-expanding medicines” for depression and anxiety at the University of Wisconsin-Madison. (4)

Since 2000, the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit based in Santa Cruz, California, has been funding clinical trials of MDMA for subjects with PTSD, mostly veterans, but also police, firefighters and civilians. In November, the FDA approved large-scale Phase III clinical trials – the last phase before potential medicalization – of MDMA for PTSD treatment. MAPS, which has committed $25 million to achieving that medicalization by 2021, also supports or runs research with the pharmaceutical extract of the psychoactive African shrub iboga. The organization is additionally funding a study of MDMA for treating social anxiety in autistic adults, currently underway at UCLA Medical Center. Another study, using MDMA to treat anxiety in patients with life-threatening illnesses, has concluded.

Other Influential groups are going full steam ahead with LSD and psilocybin research. Perhaps the most influential among them is David J. Nutt, who heads the Psychedelic Research Group in the Department of Medicine at the Imperial College, London.

In a recent scientific report in Nature (doi:10.1038/s41598-017-13282-7), Nutt and Colleagues  measure the effectiveness of psilocybin with functional magnetic resonance imaging (fMRI) . They found that treatment with psilocybin produced rapid and sustained antidepressant effects.

Ironically, issues regarding opioid use for depression were mitigated largely by the introduction of effective antidepressants half a century ago. But we are now being forced to face them again, largely because of the unmet need of many patients with refractory depression and suicidal ideation. Will the use of hallucinogens and other “illegals” follow suit?

When Ken Kesey and his band of merry pranksters began to synthesize and ingest LSD and psilocybin in the 1960s, they thought they had stumbled upon a utopian panacea. For those of us working 50-years in the future, the overarching question seems to be, how can we reconcile these two disparate worlds? If legal psychiatric research into new therapies is seen to contribute to the opioid deaths throughout America, there will be a heavy price to pay. This potential price tag was not the going “Back to the Future” that any of us had hoped for.

 

1. Yovell Y, Bar G, Mashiah M, et al: Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. Am J Psychiatry 2016; 173:491–498
2. Bodkin JA, Zornberg GL, Lukas SE, et al: Buprenorphine treatment of refractory depression. J Clin Psychopharmacol 1995; 15:49–57
3. Ehrich E, Turncliff R, Du Y, et al: Evaluation of opioid modulation in major depressive disorder. Neuropsychopharmacology 2015; 40:1448–1455
4. Schatzberg AF, DeBatttista C; The 2018 Black Book of Psychotropic Dosing and Monitoring. Psychopharmacol Bull 2017; In Press

 

Key words: hallucinogens, MDMA, ketamine, LSD, psilocybin, opioids, opioid epidemic, Alan F. Schatzberg, David J. Nutt, Psychopharmacology Bulletin, Multidisciplinary Association for Psychedelic Studies, MAPS, refractory patients