Not surprisingly, opinions also diverge on whether psychedelic drugs have therapeutic potential. Earlier this year, a survey from The Harris Poll found that 65% of Americans with anxiety, depression or PTSD believe that drugs such as the classic psychedelic psilocybin and the empathogen methylenedioxymethamphetamine (MDMA) should be available for therapeutic use. The compounds remain Schedule I drugs but could find FDA approval in the coming years.
Mental health professionals have tended to view psychedelics skeptically after they were illegal in the 1970s. A 2018 survey in The Journal of Nervous and Mental Disease found that psychiatrists tended to view psychedelics as “potentially hazardous and appropriately illegal for recreational purposes,” but a “large minority” were upbeat about their potential use in psychiatric treatment.
One factor driving interest in the therapeutic potential of psychedelics is surging rates of anxiety and depression. Almost two-thirds of Americans were at least somewhat anxious about the safety of themselves or their families in 2021, according to a survey by the American Psychiatric Association. In 2020, 27.8% of U.S. adults had depression symptoms, according to a study in JAMA. Before the pandemic, 8.5% of U.S. adults did.
While the use of antidepressants has ramped up in recent decades, rates of depression have increased.
While psychedelics may help address challenges such as anxiety, depression and PTSD, evaluating their potential requires more data, considerable education and clear frameworks for patients and physicians, said Dr. Samoon Ahmad, a New York City-based psychiatrist and co-author of Medical Marijuana: A Clinical Handbook and the author of Coping with COVID-19: The Medical, Mental, and Social Consequences of the Pandemic.
In the following interview, Ahmad discusses the difficulties involved in studying the potential benefits and risks of drugs with a history of recreational use. He also touches on the need to develop and test therapeutic frameworks to optimize the therapeutic benefit of psychedelics.
The following interview has been lightly edited.
Drug Discovery & Development (DDD): What piqued your interest in the therapeutic potential of psychedelics?
Ahmad: My interest in psychedelics grew as an offshoot of my work related to medical marijuana.
I went to medical school in the early 1980s, which was a time when there was very limited or little information or attention paid to anything in the cannabis world. That’s still true even today. As a point of reference, only 5% of medical schools have a curriculum that addresses cannabis.
I also think the political debate about marijuana has cast such a long shadow over the scientific study of it that it has become quite challenging to separate fact from fiction.
You also have this notion of cannabis as a Schedule I drug, which associates it with abuse and dependence without any medical use.
Working in the inner city hospital for decades, I’ve seen that 70% to 80% of those I might treat with severe and persistent mental illness have comorbid substance use.
At that time, I had this idea that cannabis helps treat symptoms associated with terminal illness or cancer, but again, my experience was that it’s a heavily abused drug.
Now, I have a practice where I see professionals, some of whom use cannabis. But the level of dysfunction was not the same as what I saw in the inpatient unit. So I realized there must be more to it than meets the eye.
There are inherent risks associated with cannabis, especially in adolescence. However, it’s important to weigh those risks and benefits based on context.
To reach that understanding, I had to have a basic understanding of the plant myself. When I started looking for that information, I was amazed at the lack of unbiased and scientific data I could read in one place. To make a long story short, that was a major impetus to write a book on medical marijuana for physicians and clinicians. When looking for a partner in crime, I found Dr. Kevin Hill, an addiction psychiatrist at Harvard. He has worked with the World Health Organization and NFL on cannabis policy decisions.
Writing the book taught me that cannabis was part of the larger constellation of so-called Schedule I drugs.
DDD: What insights did you glean from researching the political climate that led to cannabis and psychedelics being classified as Schedule I drugs?
Ahmad: In the late 18th and 19th centuries, there were tinctures of opium available all over in U.S. pharmacies.
There has long been a political angle pertaining to drugs.
But if you look at the research on psychedelics and the historical perspective of spiritual awakening with shamans, there is sort of a third voice on the topic. That provides an alternative to the sometimes myopic lens of culture and society.
To keep some control of society, you want myopic control. Politics sometimes trumps science. This is not new. Look at Harry Anslinger, who in the 1930s was the commissioner of the Federal Bureau of Narcotics — the equivalent of the Drug Enforcement Agency. Anslinger was one of the first people to look at how the media can play a role in demonizing drugs with a history of recreational use. All of these stories started coming out about how drugs disrupt people’s lives; ultimately, politicians, clinicians, physicians and everybody got on board with that. When the Controlled Substances Act came along in 1970, practically nobody questioned the legislation.
DDD: What would it take to add more nuance to discussions about psychedelics for potential therapeutic use?
Ahmad: If we are to understand psychedelics, cannabis and all of these things moving forward, there must be a well-educated community. You can’t just expect the medical community to say, ‘Let’s look at the double-blind studies.’ You have to educate people. Otherwise, we’ll see backlash like what we saw with the hippie movement. If that happens, all medical usefulness will go down the drain because people tend to look at the dramatization rather than risk-benefit analysis. Benzodiazepines, opioids and amphetamines are used every day in medical practice. They all have risks. To minimize that risk, you need to educate people. Unfortunately, about 5% of the medical students are educated about cannabis and fewer than that on psychedelics.
DDD: During the pandemic, there’s been some backlash against cannabis with an increase in stories about its potential to be addictive or trigger psychosis in some individuals. What is your take on that topic?
Ahmad: It is important to point out a few things. If you look at the cannabis plant as such, it has 500 ingredients in it. We only really talk about THC and CBD.
If you go back 25 to 30 years, the ratio of THC to CBD was about 4:1. CBD antagonizes the intoxicating effects of THC. Today, you’re looking at a 20:1 ratio of THC to CBD. Cannabis is a lot more potent.
And it is now to the point where there are products, such as “shatter,” with a THC to CBD ratio of 80:1. If a person who is not used to something like that takes it, are they likely to become psychotic? Absolutely. No question about it.
The dose matters. It’s analogous to clonazepam, a benzodiazepine. 0.5 mg of clonazepam has medical utility. Taking 10 mg could put you into a coma or cause respiratory arrest.
Number two, with the adolescent brain, the brain is still developing. We understand that synaptic pruning is taking place. High-potency marijuana can disrupt those pathways in many ways and cause — with long-term regular use — cognitive dysfunction and psychotic symptoms. It can lead to long-standing psychotic disorders — especially in adolescents with a family history of psychotic disorders.
But cannabinoids also can have anti-inflammatory properties. They can help manage pain and reduce end-of-life anxiety. To say all of these things don’t count minimizes the impact of these products.
During COVID, people were sitting at home. Alcohol consumption was through the roof, and some people used cannabis. There were a lot more overdoses as well. People were more depressed and anxious. And being isolated, they didn’t recognize their habits’ impact on their daily lives because there was less objectivity. In pandemic lockdowns, there were a lot more accidents. But it has to be put in context. And I think the point is, how do you balance that equation?
DDD: How much potential do you think psychedelics could have when used in a controlled environment?
Ahmad: A very good colleague, Dr. Stephen Ross, at NYU Grossman School of Medicine, has been doing psychedelic research. He has described the whole process of how psychedelics should be used. We’re not talking about going underground, taking something and imagining you will get well. We’re looking at addressing specific symptoms like PTSD, anxiety or depression. People need to understand how the research is being conducted.
Dr. Ross has described how psychedelics can be used in a controlled environment. It’s something like a living room experience but with professionals who walk patients through the experience ahead of time. Patients work on defining their intention beforehand. Physicians do a medical workup, taking patients’ vital signs. The staff asks patients how they are feeling. Mindset and setting are going to make a huge difference with psychedelics.
The staff gives patients a pill and works to optimize the experience. They play background music and put eyeshades on the patients. Some patients taking psychedelics panic. The staff is there to give them support. Sometimes in extreme circumstances, they can use medicines to negate the effect of the psychedelics.
The process could take several hours. There is a constant integrative psychotherapeutic interaction that’s taking place.
In research on the use of psychedelics for treating areas such as PTSD, depression or alcoholism, patients sometimes refer to the experience as one of the most amazing spiritual awakenings of their lifetime.
So, I think people need to understand that there is a defined process. This is not something you do on your own to see if it will have a psychotherapeutic benefit.
DDD: How mature do you think the therapeutic frameworks are for clinical trials involving psychedelics?
Ahmad: To be very honest, nobody knows right now. And that’s been a huge debate right now related to translating psychedelics into real clinical practice. Because you obviously cannot do this in outpatient settings. Who will sit with you for six to eight hours holding your hand? It probably will have to be in very controlled clinical settings — either an academic institution or other places staff available to address any issues that arise.
The second part is how do you certify physicians or other clinicians? Is it through MAPS or other organizations? Will academic institutions take the lead on this?
Nobody knows what the right approach is because we are still in Phase 2 and Phase 3 trials. There is no clear roadmap right now.
Most of the trials to date have enrolled a small number of people. But you need a huge amount of data to look at all the outcomes and get approval from the FDA.
If you look at the data, for example, on MDMA in PTSD, it’s remarkable in terms of people getting over their post-traumatic stress symptoms. You used to have a prolonged exposure therapy model for PTSD. You’re basically shortcutting that prolonged exposure therapy through an MDMA experience. The same goes for psilocybin and existential crisis at the end of life in cancer patients.
Johns Hopkins is studying the use of psychedelics on smoking cessation.
DDD: Are you optimistic about the potential societal benefit psychedelics could have in treating anxiety, depression, PTSD and so forth?
Ahmad: No question about it. Any discovery can impact not only society but the economy. In some cases, though, you might hurt the economy. So what are the forces that are going to prevent this from happening? And then there is this tendency for the media towards over-dramatization, or only looking at one aspect of things. That’s a big issue that needs to be resolved. We need to know the benefits, what kinds of clinical settings are required and who will pay for these therapies? What does the cost-benefit analysis show? Is it something for the affluent? Many people with PTSD, for instance, are veterans.
I do a lot of work with obesity, and I tell people that if everybody started to eat healthy tomorrow, there could be an economic collapse. Demand for corn, soy, sugar and processed food would plummet. So there has to be a gradual reassessment process.
DDD: What kind of education do we need to evaluate the potential of psychedelic-inspired drugs in a therapeutic context?
Ahmad: Before you embark on regulating something or opening something up, there has to be massive education at a fundamental level in the society and community. This is similar to what we’ve seen with issues with obesity and smoking.
You cannot dictate at the very top what people should do. We saw this with COVID. We really need education at the grassroots level.
Again, if you look at cannabis, it’s more detrimental before the age of 25 when used recreationally for many people. You really need to educate young people because, if you don’t do that, you see the harm but don’t see the potential benefits for other demographics. If you see the psychedelic floodgates, you could see more people going psychotic, and it will backfire. Then, every medical advantage could go down the drain with the backlash.
We also need to address these issues in the everyday curriculum of medical students.
If patients can’t get information from their doctor, where will they go to get it? Dr. Google. And they’re going to read every kind of nonsense there. They’re going to make up their own mind.
The word “doctor” in Latin means “teacher.” If we don’t teach our patients, we can’t help them. So I advise all clinicians — even if they never prescribe cannabis or psychedelics to a patient, you still need to be aware of these educational aspects. Doctors should be able to advise patients on drug interactions, the impact on labor and other conditions. I think it has to be across the board.
Filed Under: Psychiatric/psychotropic drugs