Ketamine, Shrooms Show Promise in Treating Mental Illness

By Charlie Tetiyevsky on July 5, 2017

In the past few years studies have emerged praising various alternative therapies for the treatment of recurrent depression. These include intravenous infusions of the party drug and FDA-approved anesthetic ketamine for treatment-resistant depression, eight-hour-long therapy sessions on ecstasy for anxiety in cancer and other life-threatening cases, and LSD therapy for those who are dying. Various illicit drugs are being brought back into psychiatric and research contexts after having been shut out for decades, and now psilocybin mushrooms have joined the recent resurgence of interest in psychedelics and hallucinogens for use in psychiatry. A recent study by NYU Langone Medical Center found that a magic mushrooms therapy session “clinically significant[ly] reduc[ed]” depression and anxiety in cancer patients in “about 80%” of studied cases, “a response sustained some seven months after the single dose.”

A larger, simultaneously released study at Johns Hopkins University showed similar promise on those with cancer. The choice of cancer patients for the trials has to do with the high rates of incidence of mental illness (“up to 40 percent of patients,” the New York Times reports) and its surprising resistance to traditional treatments that can work for those with such mental illnesses in other contexts. A form of treatment referred to as “psychedelic therapy” involves going through psychotherapy during a trip and then sleeping the rest of it off in a treatment facility. 

Research on psychedelics as treatment for mental illnesses like obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and depression, among others, began in the 1950s with Sandoz Laboratories’ “widespread distribution of LSD to researchers.” In the mid-60s, “more than 1,000 peer-reviewed clinical papers detailing the use of psychedelic compounds […] were published,” with a number of “proponents [like Timothy Leary] believ[ing] that psychedelic drugs facilitated [the] psychoanalytic process[,] useful for patients with problems that were otherwise difficult to treat.” (It’s important to note that these early trials are not up to modern methodological standards.)

Due to the classification of psychedelics as Schedule I illicit drugs, what amounted to a research ban kicked in by the early 1970s—an action criticized for, among other things, being colonialist because of its restriction of traditional substances like ayahuasca that are important to a number of indigenous cultures. In addition to the cultural implications, such restrictions also meant that psychiatric research on the substances slowed to a halt until around 2000—and such studies are still often, if not always, refused government funding and left to rely on “private donations.”

Some doctors are wary of the research altogether despite its promise, warning that it has echoes of studies that kickstarted another burgeoning medical—and now non-medical—sector. Dr. William Breitbart, chairman of Memorial Sloan-Kettering Cancer Center’s psychiatry department, “questioned this use of cancer patients” in the study, telling the New York Times of his concerns that the drugs are only palliative and should not be used in those without cancer. “Medical marijuana got its foot in the door by making the appeal that ‘cancer patients are suffering, they’re near death, so for compassionate purposes, let’s make it available’ […] and then you’re able to extend this drug to other purposes.”

The concern makes sense for a number of reasons: Patients with serious mental illnesses like bipolar disorder and schizophrenia can find their conditions exacerbated by psychedelic treatment, and the nature of the drugs themselves can cause issues for those with dopamine imbalances. Treatments using ketamine for depression unaffected by antidepressants and more extreme measures like electroconvulsive therapy (ECT)—an updated version of shock therapy that’s notorious for having been performed without general anesthesia—can result in dopamine-based addiction because ketamine triggers the body’s reward system in addition to “rebalanc[ing] certain brain chemicals pertaining to mood.” It’s a delicate situation, with clinicians needing to weigh the dangers of untreated depression against the risk of addiction to something like ketamine (which, like any addiction, brings on its own depressive symptoms).

But ketamine has still been making its rounds in the mental health community, a supposed beacon of hope for those whose depression hasn’t responded to standard treatment and who have either not pursued or unsuccessfully completed cognitive and behavioral modification programs (many of the options for treatment-resistant depression involve these last two elements, though understandably it’s extremely difficult to stick to self-improvement methods that may help depression when it’s that mental illness which is getting in the way—an agonizing cycle to break that takes a marked amount of fortitude if not psychiatric intervention). Ketamine clinics—places where patients can go to get intravenous infusions of the drug regularly (to maintain its anti-depressant qualities)—have emerged throughout the U.S., but “some of those clinics,” as Time writes, “aren’t run by psychiatrists or mental health professionals [but rather] by anesthesiologists and pain physicians who may not have as refined training about how best to use ketamine for depression.” Clearly concern over the intentions and actions of pain physicians in particular is nothing if not justified considering the prevalence of pill mills in places like Florida. 

Dr. Charles Nemeroff, Chairman of Psychiatry and Behavioral Sciences at the University of Miami and Chair of the American Psychiatric Association, told Time that he is concerned that “because [ketamine] is a drug of abuse” people should be “screened for drug abuse.” His is a reasonable point that unfortunately doesn’t acknowledge that even those without previous drug abuse can become trapped by the pattern of dopamine release connected to drugs stimulating the “reward” center of the brain, the mesolimbic pathway. (This part of the brain is connected to the olfactory system, which explains why smell-based triggers present such an issue for addicts. It’s been shown that “addiction, schizophrenia, and depression all involve distinct structural changes within the mesolimbic pathway.”)

Nemeroff also explains the uncertainty of having to work with drugs requiring multiple treatments like ketamine without data “on the safety or efficacy of using [the drug] long-term” and when, or if, to cease treatments: “If we give ketamine to someone who is suicidal, and they’re no longer suicidal, do we let them go? What happens the next day or two days later? Does the suicidality come back? These are the kinds of questions we need to know the answer[s] to.” As of March 2017, “only about 368” people with depression had “taken the drug in clinical trials,” a number not even approaching a typical FDA-approved clinical study, and “experts [still] do not know the best dose for treating depression.”

Dominic Sisti, assistant professor in the Medical Ethics and Health Policy department at the University of Pennsylvania, is also concerned “that off-label use is not being properly monitored in […] a vulnerable patient population.” Sisti told the Lancet that he thinks “the FDA should set up a voluntary reporting system [for ketamine clinics] to track outcomes or adverse events so that some data can be gathered in the field on the safety and efficacy of ketamine for depression.”

The more practical outcome of all of this is that drugs like ketamine, when studied, can be pared down into just their useful clinical elements (the way that cannabis and industrial hemp have been distilled into CBD for epilepsy and other medical cases that do not benefit from THC). The National Institute of Mental Health studied animal brains to take a look at what specifically is the therapeutic element in ketamine. Researchers discovered, as Time reported, “that [an element in] ketamine leads to the side effects of dependence and dissociative thinking by blocking a brain pathway called NMDA, which affects mood” via the neurotransmitter glutamate. But one of ketamine’s metabolites—something that it breaks down into after time—“remain[s] in the body for days after the drug is taken” and “appears to [be what triggers] the antidepressant effects of ketamine […] without the side effects and addictive potential [of the full drug.] If drug developers can find a way to mimic the metabolite, and provide it in just the right dose, ketamine could become an appealing treatment [and] could even be used early in a person’s depression history [to prevent] unnecessary suffering.” 

Although the dissociative episodes—the trips—caused by ketamine are considered a negative side-effect, David Feifel, professor of psychiatry at UCLA San Diego and “one of the first clinicians to use ketamine-off label to treat depression,” explained to the Lancet that no one in his experience had stopped treatments because of the “hallucinations, dreams, and out-of-body experiences […] sought after by recreational users,” and that they are occasionally a useful part of the treatment. “More often than not, patients find the trip to be positive, or even spiritual, and believe it is an important component of the antidepressant effect they experience afterwards.”

It’s not surprising to hear about trips being useful psychologically—anyone who’s either had a good trip or heard about them knows that they can be a reparative and spiritual experience given the right conditions, and presumably a clinical setting (with a psychiatrist trained in treatments, not simply an anesthesiologist or a nurse in an infusion clinic) would near-guarantee this sort of positive experience by design. 

Anecdotal evidence about psychedelics and hallucinogens like ketamine support the idea that they can reverse harmful thinking patterns and fears, with Australian shaman (you’re permitted to roll your eyes) Boaz detailing his own unmonitored experiments with drugs like psilocybin and DMT, obviously a non-clinical context for use that is dangerous for those already dealing with mental health issues since a bad trip in an uncontrolled environment can lead to dire consequences. Boaz also thinks that avoiding drug abuse requires that you “just… remain aware of what you are doing." This is an offensive suggestion for anyone who’s slipped into addiction for reasons other than a lack of awareness, like, for example, due to dysregulation in the mesolimbic pathway—something with a much higher incidence among those with co-occurring mental illnesses, referred to as “dual diagnosis” cases, which often require intensive outpatient and occasionally inpatient hospitalization.

It’s reasonable that these illicit drugs would reap some medical benefits since lab-created psychedelics and hallucinogens more frequently than not were synthesized for research and clinical purposes. It’s going to be a long road to make up for the decades of study that were waylaid by overreaching drug laws making their way into the medical field, but it’s heartening at least that there has been a resurgence of interest in treating mental illness, which affects “nearly 1 in 5 Americans” every year. Forty-five percent of all instances of Major Depressive Disorder do not respond to antidepressant treatment, and to pretend that this is not a significant problem in our society is to relegate these people to seemingly (and often actually) endless suffering. It’s not universal mental health care, but it’s a start in the right direction—as any move forward from where we currently are would be.

Mushroom photo credit: Wikipedia.

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