Hallucinogens, starvation, and magnets: A new cure for depression?

What do hallucinogens, starvation and magnets all have in common? No, they’re not the key ingredients for a wild and crazy weekend; they are all potential alternative treatments for depression that are being explored by researchers and clinicians alike.

Scientists have long known that the serotonin theory of depression is imperfect, yet few treatment options are available beyond the standard course of cognitive-behavioral therapy and selective serotonin reuptake inhibitors (SSRIs). In my new piece for Pacific Standard, I explore recent research that has emerged looking at some potential alternatives for depression that are rather… unconventional.

This includes giving people psilocybin, the active ingredient in so-called “magic” mushrooms, which also boosts serotonin levels and crucially taps into the amygdala, the brain’s major emotional center. Another possible avenue involves boosting ghrelin levels in the brain, a hunger hormone that may also play a role in protecting neurons from the destructive effects of stress, particularly in the hippocampus. Alternatively, using high-powered magnets, researchers and clinicians are able to activate certain key parts of the brain that can potentially lead to a suppression of other over-active emotional regions, turning down our feelings of anxiety or depression.

While none of these options is perfect, they do provide an encouraging new perspective, thinking outside the box to treat this condition that will afflict at least one in ten of us at some point in our lives.

You can check out the full story in Pacific Standard here.

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Psychiatry and psychedelia

Timothy Leary, the influential psychologist who popularized the use of LSD in the 1960s, is a polarizing figure in the debate on psychiatry and psychedelic drugs. While revered by some as the father of psychedelic research, he is reviled by others for his unconventional research methods, which culminated in Leary’s lab, the Harvard Psilocybin Project, being shut down by the university in 1963. Following this setback, Leary established a private laboratory in a mansion in upstate New York where he continued conducting studies on his friends and followers. Leary’s previously unseen recordings and notes from this period have recently been purchased and published by the New York Public Library, for the first time giving us insight into the ground-breaking work done with these then novel substances.

The backlash to Leary and his colleagues’ extremist views regarding drug use, religion, and politics (Richard Nixon at one point called Leary “the most dangerous man in America”) potentially discredited any real benefits psychedelics may have in therapy for over 40 years. Experimentation and research with LSD, psilocybin (commonly known as hallucinogenic or “magic” mushrooms), and other psychedelic substances have been highly stigmatized and virtually impossible to conduct in a responsible laboratory setting. However, the restrictions against such research have gradually been lifted, and new studies are cautiously popping up heralding the clinical benefits of drugs like psilocybin and MDMA, or ecstasy.  These drugs are thought to help individuals who suffer from severe anxiety, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and depression when paired with talk therapy methods. The effectiveness of these drugs is thought to lie in their ability to engender feelings of empathy, love, and connectedness, fostering a sense of unity and compassion for oneself and fellow man. These feelings may potentially create an easier, more open environment for patients to discuss their concerns, while safely being guided by clinicians on a therapeutic trip.

Some of the most notable research coming out of this renaissance is being conducted at John’s Hopkins University, led by Dr. Roland Griffiths. Griffiths has shown that psilocybin can be used to effectively reduce levels of depression and anxiety in terminally ill cancer patients, anecdotally helping some patients to accept and come to terms with their approaching mortality.

Another influential use for this type of research is in patients with PTSD. With the recent announcement that antipsychotic drugs–frequently prescribed to help treat PTSD in combat veterans–are no more successful than placebos at improving symptoms, it seems that a new method is needed to help those suffering from severe trauma. Antidepressants are already known to be ineffective in treating PTSD, and doctors were hoping that antipsychotic medication, a stronger affecter of mood, would be more successful at treating the associated symptoms, like flashbacks, memory suppression, outbursts of anger, anxiety, anhedonia, and depression. However, after six months of treatment, only 5% of patients who received the drug had recovered, a number that was statistically negligible and not significantly different from those who had received a placebo.

Some researchers are now looking at more unconventional methods, such as psychedelics, as a potential treatment for PTSD. Clinical researchers both in the US and in the Netherlands have shown that MDMA can be effective at reducing PTSD symptoms in survivors of rape or other traumatic events. Neurologically, MDMA stimulates serotonin in the brain, a neurochemical linked to feelings of happiness and the depletion of which is commonly attributed to depression. This activation takes place throughout the brain, but much of it is focused in the dorsal lateral prefrontal cortex (dlPFC), a region involved in higher order cognition, memory, and associative learning. Simultaneously, there seems to be a decrease in amygdala activity, an area involved in fear and emotion. Taken together, these two changes in neural activity are thought to increase memory and improve rational, cognitive coping of the traumatic event while down-playing the aversive negative emotions connected to it. Therefore, an individual would be able to replay the painful details of a memory and rationally analyze and come to terms with them, facilitated by a boost in mood from serotonin and disconnected from the typical painful affective responses. This could potentially help a patient “relearn” their associations with this memory, thus allowing them to lose the negative and recreate positive affective associations for these recalled experiences.

However, just as there are side effects with any drug, so there are too with MDMA. The most notable and potentially harmful one is a resulting decrease in serotonin after the high has worn off. When the brain is flooded with a neurochemical, it regulates itself to become less receptive to this neurotransmitter, adapting to re-obtain homeostasis in the chemical levels in the brain. Therefore, the brain becomes relatively depleted of serotonin in the days after taking MDMA, and after multiple uses (or abuses) of the drug this effect can become pervasive and long-lasting. While the amounts of depletion are not particularly severe after minimal use, this temporary loss could be potentially devastating in a patient who is already struggling with depression or anxiety.

Banning potentially valuable clinical research because of social concerns and constraints only hurts scientific progression and the community at large. However, it is important to keep in mind that these psychedelic substances are powerful drugs with potentially severe consequences. They should be investigated, as their benefits to clinical populations could be immense, but they should still be used carefully as much is still unknown (just as much as unknown about most drugs, prescription or otherwise) about their mechanisms and effects. Responsible research is the best way to investigate the therapeutic possibilities of these drugs, and the existence of methodical record taking like Leary’s can only help us in our quest to understand these substances and their effects on the mind.