For many, antidepressants are a way of life — both essential to normal human functioning and still not quite good enough. But, a new wave of research suggests that psychedelic drugs, unlike traditional antidepressants, may be able to provide long-lasting relief quickly for those dealing with some of our most common mental illnesses.
For patients looking at a lifetime's worth of selective serotonin reuptake inhibitors (or SSRIs) and the side effects that come with them, a one-and-done session with LSD may seem pretty appealing. But, without doctors able to prescribe these substances, people are turning to illegal means to self-medicate, creating a possibly unsafe situation for the already mentally ill.
Cam, a 21-year-old chemical analyst from Okanagan Valley, British Columbia, has tried seemingly every medication under the sun to ease his anxiety and bipolar disorder: Lithium, Zopiclone, Citalopram, Ativan, Clonazepam, Seroquel, Resperidone, and Valium, just to name a few. But, he says all of them made him feel withdrawn, hollow, and “meh.”
Nothing helped quite like lysergic acid diethylamide — LSD. After trying it recreationally at age 16, Cam says he now self-medicates with LSD every 10 months or so when his anxiety becomes too much. "I had never been able to delve deeper into my own psyche than with the assistance of LSD," he says. "I was able to come to terms with the overly-high expectations I had set for myself...and accepted that they were more to please my family [than] myself. And, that my family only wanted my happiness anyway."
Stories like Cam's have been capturing the attention of researchers. Now, scientists are beginning to pick up where they left off when the restrictive 1970 Controlled Substances Act and the other regulations that followed began to keep psychoactive substances out of the hands of scientists — and the rest of us. Now, after spending decades on the shelves, these drugs are once again under the microscope. And, they're cracking minds wide open.
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Current Antidepressants
According to the most recent available statistics, around one in 10 Americans over the age of 12 takes an antidepressant — most for over two years. Some of the most commonly-prescribed drugs are SSRIs such as Zoloft and Prozac. Dennis McKenna, PhD, explains that SSRIs work by blocking the serotonin transporter, keeping the serotonin that’s released in the synapse. Serotonin is involved in a myriad of biological processes, so interfering with its signaling can, understandably, cause a lot of side effects — from short-term nausea or dizziness to long-term weight gain, agitation, insomnia, and reduced sexual drive.
Contrary to traditional thinking, neuroscientists realized about a decade ago that the brain is constantly in flux. When you’re learning something new, it needs to make a physical change — a new pathway — for that knowledge to stick. Current thinking suggests that every time you revisit the idea, that new pathway gets stronger, possibly until the thought becomes automatic.
Both depression and anxiety are characterized by repetitive thought patterns, such as immediately jumping to the worst-case scenario or negative cycles of self-doubt. Identifying and learning to modify these patterns is often an essential part of therapy. But, there's evidence that by acting on serotonin, SSRIs can help make changing those circuits a little easier — or at least start the the process. This is one possible reason why it can take weeks or months of antidepressant treatment before patients see any psychological changes.
However, other substances may be better suited to encouraging large-scale changes much faster.
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The Alternatives
Some might say the resurgence of research into the therapeutic potentials of controlled substances started with MDMA, which works on the same serotonin transporter that SSRIs target. But, instead of blocking the reuptake of serotonin, it holds the door wide open, causing a flood of serotonin into the synapse, explains Dr. McKenna. Now, there are large-scale investigations into MDMA’s potential for treating post-traumatic stress disorder (PTSD). These studies have found that therapy sessions — with the assistance of MDMA — can be the perfect catalyst to work through the paranoia and anxiety characteristic of PTSD. MDMA may help with other types of anxiety as well. "MDMA helped me overcome social anxieties," says 18-year-old reddit user (and r/drugs frequenter) Shirrapikachu. "I had an entirely new perspective on the world and how you interact with people. I learned that people are a lot more accepting and kind than I originally thought, and a little confidence goes a long way in making new friends and approaching people," she says. "From that point on, I basically faked it until it became a reality, and quit caring so much about how people saw me." Mark, another 19-year-old reddit user, first tried ecstasy at a festival two years ago before experimenting with the drug's purer form, MDMA. He describes similar insights: "I learned that those 'self-preservation' thoughts that stop you from doing stuff and cause anxiety are not permanently a part of me," he says. "Doing a drug that makes you a happy version of yourself, without anxiety, will teach you a lot about how to reduce those aspects in your [normal] life." Classic psychedelics have shown similar benefits. Researchers have found that psilocybin — the psychoactive component in psychedelic mushrooms — can reduce the existential, end-of-life anxiety in dying cancer patients. Similarly, LSD has been found to reduce anxiety in conjunction with therapy in double-blind, placebo-controlled studies. And, both of these drugs target the serotonin receptors. Much of the work with MDMA has been spearheaded by the Multidisciplinary Association for Psychedelic Studies (MAPS). But, the Heffter Research Institute (of which Dr. McKenna is a co-founder) has organized the majority of psilocybin work. Unlike when they were using SSRIs, people in these trials felt real change after just one session. And, this wasn’t just feeling better; big existential questions were being answered. As Shirrapikachu put it, "LSD trips have been tough and magical, and helped me make huge leaps in my therapy. Years of progress made easy." When Adrienne, 31, a social worker, first tried LSD, she was in the middle of one of the most difficult periods of her life. "I could not look in the mirror without crying and wanting to kill myself," she says. But, 10 years ago, she had a life-changing acid trip. Her mind went straight to a photo from her childhood, when she was about seven years old. "I'm sitting on a rock by a lake, staring at the camera with this awesome, confident smile," she says. "All I could think of is that I'm still that little girl somewhere inside, and I just have to find her." Obviously, unless you're taking part in a study, your therapist probably isn't going to be keen on you dropping acid during your session. And, for the time being, your insurance definitely isn't going to cover your MDMA costs. But, in the future, Dr. McKenna says all of these substances would ideally be taken under strict supervision and guidance. “You need the assistance of a therapist to help integrate that experience,” he says. “This is never going to be like, ‘Take two and call me in the morning.’” “If you did take two," he adds, "chances are you’d forget to call in the morning.”
Some might say the resurgence of research into the therapeutic potentials of controlled substances started with MDMA, which works on the same serotonin transporter that SSRIs target. But, instead of blocking the reuptake of serotonin, it holds the door wide open, causing a flood of serotonin into the synapse, explains Dr. McKenna. Now, there are large-scale investigations into MDMA’s potential for treating post-traumatic stress disorder (PTSD). These studies have found that therapy sessions — with the assistance of MDMA — can be the perfect catalyst to work through the paranoia and anxiety characteristic of PTSD. MDMA may help with other types of anxiety as well. "MDMA helped me overcome social anxieties," says 18-year-old reddit user (and r/drugs frequenter) Shirrapikachu. "I had an entirely new perspective on the world and how you interact with people. I learned that people are a lot more accepting and kind than I originally thought, and a little confidence goes a long way in making new friends and approaching people," she says. "From that point on, I basically faked it until it became a reality, and quit caring so much about how people saw me." Mark, another 19-year-old reddit user, first tried ecstasy at a festival two years ago before experimenting with the drug's purer form, MDMA. He describes similar insights: "I learned that those 'self-preservation' thoughts that stop you from doing stuff and cause anxiety are not permanently a part of me," he says. "Doing a drug that makes you a happy version of yourself, without anxiety, will teach you a lot about how to reduce those aspects in your [normal] life." Classic psychedelics have shown similar benefits. Researchers have found that psilocybin — the psychoactive component in psychedelic mushrooms — can reduce the existential, end-of-life anxiety in dying cancer patients. Similarly, LSD has been found to reduce anxiety in conjunction with therapy in double-blind, placebo-controlled studies. And, both of these drugs target the serotonin receptors. Much of the work with MDMA has been spearheaded by the Multidisciplinary Association for Psychedelic Studies (MAPS). But, the Heffter Research Institute (of which Dr. McKenna is a co-founder) has organized the majority of psilocybin work. Unlike when they were using SSRIs, people in these trials felt real change after just one session. And, this wasn’t just feeling better; big existential questions were being answered. As Shirrapikachu put it, "LSD trips have been tough and magical, and helped me make huge leaps in my therapy. Years of progress made easy." When Adrienne, 31, a social worker, first tried LSD, she was in the middle of one of the most difficult periods of her life. "I could not look in the mirror without crying and wanting to kill myself," she says. But, 10 years ago, she had a life-changing acid trip. Her mind went straight to a photo from her childhood, when she was about seven years old. "I'm sitting on a rock by a lake, staring at the camera with this awesome, confident smile," she says. "All I could think of is that I'm still that little girl somewhere inside, and I just have to find her." Obviously, unless you're taking part in a study, your therapist probably isn't going to be keen on you dropping acid during your session. And, for the time being, your insurance definitely isn't going to cover your MDMA costs. But, in the future, Dr. McKenna says all of these substances would ideally be taken under strict supervision and guidance. “You need the assistance of a therapist to help integrate that experience,” he says. “This is never going to be like, ‘Take two and call me in the morning.’” “If you did take two," he adds, "chances are you’d forget to call in the morning.”
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Of all the controlled substances that could help treat anxiety and depression, the one that's farthest along is ketamine. A recent slew of research suggests that ketamine infusions can act as a quick intervention — reducing depression symptoms often within hours — especially in chronically depressed patients who haven't responded to traditional medication. But, it's worth pointing out that researchers first became interested in ketamine's psychiatric effects nearly 20 years ago following the Gulf War, explains Glen Z. Brooks, MD. Investigators noticed that soldiers who'd received the anesthetic during surgeries were much less likely to develop PTSD than those who hadn't gotten it, despite the fact that they'd received larger wounds.
Rather than working directly on serotonin, ketamine targets our glutamate receptors, which, in turn, promotes the production of a little thing called brain-derived neurotrophic factor (BDNF). This is a protein crucial for creating and keeping new neurons alive. The full course consists of six ketamine infusions given 24-48 hours apart, followed by single "booster" infusions every six weeks or so if needed.
"After taking ketamine, I just feel more balanced and content. I'm not really depressed; I'm much less anxious," explains Marcus, 24, from Pennsylvania — who estimates that he's tried between 30 and 40 other psychiatric medications, to no avail. But, with a little ketamine? "When I try talking to people about how I feel, [they'll] say that's how they feel normally," he says. "I feel very at peace...very natural and normal as well, whereas other psychoactive drugs generally don't [make me feel that way]."
Because ketamine already has a long-established medical history as an anesthetic, doctors can give it to patients for off-label reasons without any legal issues. Dr. Brooks, who operates New York Ketamine Infusions, says the actual infusion process is pretty uneventful: It takes about 45 minutes and patients are encouraged to listen to their favorite music. Although there is some mind-body dissociation, there are no outright hallucinations.
But, the results are still dramatic. "For patients that are suicidal, and many of my patients are," says Dr. Brooks, "they can begin to see some relief in just two to three hours...to the point where they can’t even imagine why they would have been suicidal."
What's Coming Up
Truly accepting these drugs as therapeutic tools would require big changes at several levels — not just in public opinion. Psilocybin, LSD, and MDMA are all schedule I drugs, meaning the federal government considers them both highly addictive and without any accepted medical benefit. Scheduling has made it difficult to access these drugs — even for scientists. As LSD researcher David Nutt, PhD recently pointed out, they've been "banned effectively from research for 50 years."
And, pharmaceutical companies can't necessarily justify the monumental costs needed to research and bring a drug to market if they can't have the rights to it. To tackle that, AstraZeneca has started looking at analogues of ketamine, but how they would handle a psilocybin-like pill remains to be seen.
The way psychiatry actually happens would need to evolve as well, Dr. McKenna explains. Rather than spending 15 minutes with a patient, chatting with their therapist, and prescribing a pill, psychiatrists would have to commit to spending hours guiding patients through a full-on experience. This would also allow them to make sure patients are truly safe — although there's no definitive evidence yet to suggest LSD and psilocybin are addictive or dangerous in the long-term, bad trips can be truly traumatic.
Because most would-be patients don't have a place to do all this under doctor supervision, harm-reduction sites like Bluelight are essential. "People will do it, whether it's condoned or condemned," says site admin alasdair. "So, it's more important than ever that there are resources available to allow people to inform themselves as fully as possible before making a decision."
There has been some progress. Marijuana is still a schedule I drug at the federal level, but it's now legal for medical use in 23 states and Washington, D.C. Pot might not be a gateway drug in the traditional sense, but it has set a precedent for reexamining once-forbidden compounds in therapeutic contexts. "Medical marijuana is opening up the minds of regulators, the public, researchers, and physicians into the possible beneficial uses of schedule I drugs," says Brad Burge, spokesperson for MAPS.
Still, "physicians obtain their certifications from national regulatory bodies, and they obtain their prescription-writing power from the FDA or DEA, which are federal agencies," he says. So, even if all 50 states and D.C. had accepted legal medical marijuana use on a local level, we could still have a situation in which physicians couldn't prescribe it.
By going straight for clinical trials and FDA approval, that's exactly what MAPS hopes to avoid for psychedelics. MAPS already has phase II development underway for both MDMA and psilocybin, which requires medium-sized studies looking at both safety and therapeutic efficacy. And, just this past week, the DEA approved MAPS' new trial of MDMA-assisted therapy for the treatment of anxiety surrounding life-threatening illnesses, which is the first time the organization has looked at MDMA for this specific clinical use.
If things continue to go well, Burge says we could see FDA approval for MDMA-assisted therapy for the treatment of PTSD by 2021. Burge predicts that psilocybin would follow suit. From there, we could be looking out at a very different landscape — perhaps one in which people suffering from anxiety and depression have a more powerful arsenal of tools to choose from in their search for real relief.
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