In recent years, psychedelic drugs like LSD and psilocybin have garnered increased attention for their potential therapeutic effects. These drugs are considered relatively safe and non-addictive. But one notable side effect that has received limited attention is the occurrence of drug-like experiences after the initial effects of the drugs have worn off.

These recurring drug-like effects are called flashbacks, and symptoms include vision changes, mood changes, and derealization/depersonalization. If these flashbacks persist and cause significant distress or impairment, they might be referred to as hallucinogen-persisting perception disorder (HPPD), a condition named by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).

Study author Felix Müller and his team say that the scientific understanding of flashbacks is limited, and existing data has relied on case reports and naturalistic studies. The researchers sought to better describe flashback phenomena and HPPD by analyzing data pulled from multiple clinical trials.

The researchers collected data from six double-blinded, placebo-controlled studies that included a total of 142 participants between the ages of 25 and 65. During the trials, 90 participants received LSD, 24 received psilocybin, and 28 received both drugs. Doses varied by trial, with participants receiving between 1–5 doses of LSD that ranged from 0.025 and 0.2 mg, and/or between 1–2 doses of psilocybin that ranged from 15 and 30 mg.

Throughout the study sessions, subjects were asked to report any adverse experiences, including the occurrence of flashbacks. After the final study session, an end-of-study visit took place where subjects were again asked to describe any flashback phenomena that had occurred over the course of the study.

On the final study visit, 13 participants (9.2%) described some type of flashback experience. Of these cases, seven had occurred after taking LSD, two after psilocybin, and four after taking both substances. For 11 of the 13 participants, these flashbacks consisted of visual alterations. Three participants experienced other phenomena along with these visual effects, such as auditory or cognitive symptoms, and two subjects experienced emotional alterations only. All flashback experiences lasted from seconds to minutes, except in one case when the flashbacks lasted for hours.

The majority of participants (76.9%) reported that these flashbacks were neutral or positive experiences. Two subjects deemed them unpleasant, one of whom described a single distressing episode occurring 17 days after taking 25 mg of psilocybin.

Notably, this participant was also on day two of taking a serotonin reuptake inhibitor, which has been found to induce flashbacks in hallucinogen users. The other participant who reported unpleasant flashbacks said the experiences occurred across four days after taking 0.2 mg of LSD. In both cases, the flashback episodes did not impair participants’ daily lives and resolved spontaneously.

Müller and his colleagues also conducted a follow-up study after the final study visit. Since the studies were completed at different times, the time from the last study visit to the follow-up varied from months to years. Only one participant described the occurrence of further flashbacks, which consisted of visual alterations that occurred about 30 times in seven months. These flashbacks lasted seconds long and did not impair daily life. The researchers determined that none of the participants met criteria for HPPD at any time point, although they note that HPPD is rare and that their sample size was small.

In general, these findings suggest that flashback experiences are relatively common in LSD and psilocybin trials, with about 9% of participants reporting such effects. However, only 1.4% of participants experienced distressing flashbacks, and no treatment was needed in these cases. “Overall,” the authors conclude, “our data suggests that flashbacks are not a clinically relevant problem in controlled studies with healthy participants.”

The study, “Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants”, was authored by Felix Müller, Elias Kraus, Friederike Holze, Anna Becker, Laura Ley, Yasmin Schmid, Patrick Vizeli, Matthias E. Liechti, and Stefan Borgwardt

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Source: Johns Hopkins Medicine

Psychedelic drugs like psilocybin, an ingredient found in so-called magic mushrooms, have shown promise in treating a range of addictions and mental health disorders. Yet, there’s something mysterious and almost mystical about their effects, and they are commonly believed to provide unique insights into the nature of consciousness.

Now, a new study by Johns Hopkins Medicine researchers addresses the question of whether psychedelics might change the attribution of consciousness to a range of living and nonliving things.

The findings, published March 28 in Frontiers in Psychology, reveal that higher ratings of mystical type experiences, which often include a sense that everything is alive, were associated with greater increases in the attribution of consciousness.

“This study demonstrates that when beliefs change following a psychedelic experience, attributions of consciousness to various entities tend to increase,” says Sandeep Nayak, M.D., postdoctoral research fellow at the Johns Hopkins Center for Psychedelic and Consciousness Research and one of the researchers involved in the study.

“It’s not clear why, whether that might be an innate drug effect, cultural factors, or whether psychedelics might somehow expose innate cognitive biases that attribute features of the mind to the world.”

For the study, the researchers analyzed data gathered between August 2020 and January 2021 on 1,606 people who had had a belief-changing psychedelic experience. Participants averaged 35 years of age and were predominately white (89%), male (67%) and from the United States (69%).

Study participants completed an internet-based survey that included questions focused on belief changes attributed to a single psychedelic experience with a classic psychedelic substance (e.g., psilocybin mushrooms, LSD, ayahuasca). The survey also included questions about demographics, psychedelic use, personality, and scientific knowledge and attitudes.

The study found that among people who had had a single psychedelic experience that altered their beliefs in some way, there were large increases in attribution of consciousness to a range of animate and inanimate things.

For example, from before to after the experience, attribution of consciousness to insects grew from 33% to 57%, to fungi from 21% to 56%, to plants from 26% to 61%, to inanimate natural objects from 8% to 26% and to inanimate manmade objects from 3% to 15%.

“On average, participants indicated the belief-changing experience in question occurred eight years prior to taking the survey, so these belief changes may be long-lasting,” says Nayak.

Classic psychedelics—the pharmacological class of compounds that includes psilocybin and LSD—produce visual and auditory illusions and profound changes in consciousness, altering a person’s awareness of their surroundings and of their thoughts and feelings.

These substances produce unusual and compelling changes in conscious experience, which have prompted some to propose that psychedelics may provide unique insights into the nature of consciousness itself.

“The results suggesting that a single psychedelic experience can produce a broad increase in attribution of consciousness to other things, raises intriguing questions about possible innate or experiential mechanisms underlying such belief changes,” says Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research.

“The topic of consciousness is a notoriously difficult scientific problem that has led many to conclude it is not solvable.”

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Acid and mushroom trips may be two sides of the same psychedelic coin, according to findings from a clinical study published Friday in Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology.

Conducted by Professor Matthias Liechti at the University of Basel in Switzerland, the double-blinded, randomized, and placebo-controlled study compared the subjective and autonomic effects of psilocybin — the psychoactive ingredient in certain mushrooms — to those of lysergic acid diethylamide (LSD). Researchers observed 28 test subjects. Some were experienced psychonauts. Others had never dabbled in hallucinogens. Each underwent five different test sessions involving two different doses of LSD (100 micrograms and 200 micrograms), two different doses of psilocybin (15 milligrams and 30 milligrams), and one placebo.

A double-blinded, randomized, and placebo-controlled study compares the subjective and autonomic effects of psilocybin to those of LSD, and the results are astounding.

Acid and mushroom trips may be two sides of the same psychedelic coin, according to findings from a clinical study published Friday in Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology.

Conducted by Professor Matthias Liechti at the University of Basel in Switzerland, the double-blinded, randomized, and placebo-controlled study compared the subjective and autonomic effects of psilocybin — the psychoactive ingredient in certain mushrooms — to those of lysergic acid diethylamide (LSD). Researchers observed 28 test subjects. Some were experienced psychonauts. Others had never dabbled in hallucinogens. Each underwent five different test sessions involving two different doses of LSD (100 micrograms and 200 micrograms), two different doses of psilocybin (15 milligrams and 30 milligrams), and one placebo.

The authors cite growing interest in psychedelic-assisted therapy as one of the reasons behind their study, pointing out that while different psychedelics are now known to combat everything from anxiety and depression to post-traumatic stress syndrome, no modern study had properly evaluated the actual subjective and autonomic effects of LSD and psilocybin.

In terms of the autonomic differences, the study found psilocybin increased the subject’s blood pressure more than LSD, whereas LSD resulted in a greater increase of heart rate. Both drugs showed comparable cardio stimulant properties.

The study examined adverse effects of the psychedelics, too. No severe adverse events were observed, though a few participants suffered aftereffects ranging from headaches and nosebleeds to nightmares and restlessness. The type and quantity of the adverse events was comparable after both psilocybin and LSD trips.

Researchers also found no difference in the autonomic and adverse effects of LSD and psilocybin between male and female participants.

As hallucinogenic historians will note, this isn’t the first time a scientist in Basel made a name for himself by experimenting with LSD. The Rhine-adjacent municipality doubles as the birthplace of the acid trip. On April 19, 1943, Swiss chemist Dr. Albert Hofmann ingested 250 micrograms of LSD and rode his bicycle home as the drug’s psychoactive properties began kicking in. Enthusiasts now celebrate Hofmann’s discovery every year on April 19, a holiday which has come to be known as “Bicycle Day.”

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Last month, Health Canada’s new Special Access Program (SAP) amendment went into effect, allowing physicians to request access to psilocybin, MDMA, DMT, LSD, and other psychedelic treatments not officially approved for sale in the country. The amendment, which reversed a 2013 policy prohibiting special access to restricted drugs, signifies a positive change in the healthcare industry’s perception of psychedelics.

But while medical professionals and psychedelic advocates responded with enthusiasm, the news also ignited a few misconceptions around program eligibility and psychedelic legality.

“This [amendment] shows that Health Canada is aware of the promise of psychedelic therapy and committed to understanding more through further research,” says Dr. DJ Cook, Head of Neurosurgery at Queen’s University and Chief Medical Officer at Dimensions Healing. “But it won’t be an assured means of acquiring these medicines for therapy — there will be a threshold to gain approval.

To better understand, we dug deeper into how the program will work, who will benefit, and whether there’s potential for full legalization.

How Does the Special Access Program Work?

For several years, Canadian health care providers have relied on Health Canada’s SAP to access otherwise unavailable drugs for “serious or life-threatening conditions” — particularly when traditional paths fail to yield positive outcomes. For example, the SAP might grant access to a not-yet-approved chemotherapy drug for a patient with a rare tumor or a new antiviral for a patient with long-standing, treatment-resistant HIV.

However, requests are decided on a case-by-case basis and don’t automatically guarantee access. When a healthcare professional determines a patient may benefit from a drug that’s not yet available for sale, they must submit a request to Health Canada and wait for a decision. If approved, the manufacturer is cleared to supply the drug to the licensed health care professional to distribute to their patient.|

When it comes to psychedelics, health care providers can only access drugs from a dealer licensed under the Controlled Drugs and Substances Act (CDSA). In other words, the SAP doesn’t give carte blanche to all psychedelics from any source.

However, the SAP amendment also doesn’t require psychedelics to be dispensed in a therapy setting — which Dr. Cook says could be an oversight. “There is a key aspect to the environment and setting in which these therapies are undertaken,” he says. “Having therapists and retreat centers and therapeutic settings where patients can [take psychedelics] in a way that respects the cultural and ceremonial aspects of the therapies is critical.”

Kelsey Ramsden, co-founder and CEO of MINDCURE, agrees that integration is essential. “I think people are a bit misguided about this idea that psychedelics without psychotherapy will get the same kind of result,” she says. “Having psychotherapy paired with these drugs allows people to integrate what they learn.”

Of course, patients can choose to seek psychological therapy alongside the medication on their own, and health care professionals may even encourage psychotherapy or include it within their care plan. But, currently, it’s not required.

Who Will Likely Benefit Most from the SAP?

We still don’t know how Health Canada defines “life-threatening” regarding mental health conditions or how many failed conventional treatments are necessary before a patient can access a psychedelic drug. And we likely won’t know more until there have been a significant number of cases authorized or denied. But experts have some ideas about which conditions may be more likely to get approval.

“I think individuals in a palliative state who are experiencing death anxiety, for instance, and where there is reasonable literature supporting the use of psychedelics to treat anxiety, have a clear case,” Dr. Cook says. Additionally, he notes patients with treatment-resistant PTSD and those with a high potential for suicidality also have a strong case. “But again, the threshold and the requirements of proof are unknown.”

Without a concrete list of conditions, we can assume Health Canada will follow the data. And studies on psychedelic use in end-of-life care, Alzheimer’s care, and treatments for people grappling with post-traumatic stress do make compelling arguments.

Kelsey also believes the conditions that fall into the “serious or life-threatening” category will shift as clinical research evolves and the SAP fields more cases. “I believe that, over time, we’re going to see ’emergency’ classified as people who’ve had consistent drug overdoses, for example, and we’re going to see this expand and morph.”

Will Psychedelics Follow the Same Path to Legalization as Cannabis?

One of the biggest questions amidst the amendment’s rollout is whether psychedelics are on the same course to legalization as cannabis. However, it appears, at least in this stage, that Health Canada is treating these drugs more like a controlled medicine and less like a recreational substance.

“What we’re talking about with respect to psychedelic medicine is very different than cannabis,” Kelsey says. “Comparing the two is like comparing a Ferrari to Toyota Tercel. Both will get you places, but one is very powerful and requires a lot of experience to handle properly. Who do you want to put behind the wheel of something that performs this way?”

Dr. Cook echoes this sentiment and says the pathway to legalization for psychedelics should more closely resemble pharmaceutical development than cannabis. “I hope that there is a more metered and regulated approach to accessing the therapies,” he says.

But even with its limitations and ambiguous thresholds for accessibility, the new amendment is an exciting step in a progressive direction. It’s also a clear signal that regulators are interested in seeing psychedelics advance. And as new data moves science forward, patients’ first-hand accounts will likely sway culture toward normalization and acceptance.

“The more we have individuals who can speak to the transformative effects of psychedelics for mental health care, the better we all will be,” Kelsey says. “It’s a testament to the forward-thinking nature of our healthcare system. And for that, I’m grateful.”

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A new study will measure how the time of day during consumption influences the effects of LSD microdosing.

Announced by biotechnology company MindMed today, this study will evaluate and compare daytime and evening administration of repeated low doses — also known as microdoses — of LSD.

Low dose psychedelics expert and Associate Professor at Maastricht University in the Netherlands, Dr. Kim Kuypers, will lead the study.

Her team of researchers will be using digital measurements devices and software to evaluate the effects of LSD microdoses on neuroplasticity markers such as BDNF plasma levels and various measures of sleep, mood, cognitive performance, regulation of emotions, quality of life, and immune system response.

“Research into the practice of taking repeated low doses of psychedelics starts with the basics, looking at whether there is a time of day that influences the impact of these treatments,” Dr. Kuypers explained.

“We are investigating whether the repeated intake of lower doses could lead to a realignment of patterns of thinking that would enable individuals to access levels of self-awareness that can provide an enriched experience of life.”

In recent years, an emerging trend in the psychedelics space has been microdosing  — consuming a small fraction of what is considered a recreational dose of a psychedelic substance, usually LSD or psilocybin. The doses used are so small that they do not induce hallucinations.

To date, there is anecdotal evidence from leading tech entrepreneurs to parents who claim microdosing can boost creativity and productivity, and reduce anxiety.

However, microdosing’s potential is not fully understood due to a lack of evidence. In fact, a recent study from Imperial College London demonstrated that microdosing might be nothing more than a placebo. Researchers concluded that participants’ belief they were taking a microdose was more influential in improving their mental health than the microdose of a drug itself.

Many first-of-its-kind studies evaluating microdosing are currently underway in a bid to scientifically validate anecdotal claims about its effectiveness.

This includes an Australian analysis using neuroimaging to understand microdosing’s effects on the brain and a New Zealand study exploring how LSD microdosing may help cancer patients experiencing end-of-life distress. MindMed hopes that its new study will add much-needed evidence to support and explore the safety and benefits claimed about microdosing.

“With our innovative study design, integrating digital medicine measurement techniques with more traditional self-reporting and cognitive tasks, our goal is to provide insight on key parameters that may impact and explain the mechanisms behind low-dose treatments,” said MindMed’s Executive President Dr. Miri Halperin Wernli.

“This regimen could provide new tools to deal with various pathologies, helping to unblock pathological ways of thinking by shifting an individual’s perspective, catalyzing insights and ultimately changing problematic and habitual mindsets and behaviours.”

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I knew from the description of the invitation that I would be addressing a crowd of approximately 45 Rotarians from 40 to 70 years old, who had signed up for a morning breakfast club to learn about the writing I’ve been doing on the topic of psychedelic therapies. They were intrigued to learn more about these new treatments. The program planner found my perspective interesting, he said, noting that his members were probably “a little less High Times and a bit more Forbes.” I took that to mean that the crowd leaned conservative—at least where psychoactive drugs were concerned—and assumed it could mean opposing viewpoints from the audience about the use of currently illegal drugs. I was up for that. 

The club members sounded like an engaged and attentive group, working professionals who regularly attended these Wednesday morning author talks at 7 a.m., held on various subjects, meant to create a forum for Rotarians to share new ideas over eggs, bacon, pancakes, and coffee. The setting was also an ideal focus group for me: A utilitarian Masonic Hall—indistinguishable from countless such buildings dotted across the U.S.—and located literally on Main Street in a small town known as the “Gravenstein Apple Capital of the World.” You didn’t get more American than that. Their mission struck the right chord, too: “Rotary is a global network of 1.2 million neighbors, friends, leaders, and problem-solvers who see a world where people unite and take action to create lasting change – across the globe, in our communities, and in ourselves.”

The email invite arrived a few days after I was interviewed on The Entheogenic Evolution podcast, hosted by psychedelic specialist Dr. Martin Ball. During the show we discussed my reporting for Forbes online covering trends and breakthroughs in psychoactive drugs, as well as my booklet titled “Your Neighbors are Doing Psychedelics: MDMA” (2021). The story follows an ex-policeman named Nick Watchorn, who was part of FDA-sponsored clinical trials of MDMA-assisted therapy to treat his severe, treatment-resistant PTSD. Watchorn had suffered with the debilitating condition for 22 years after arriving on the scene of a horrific mass-shooting in Port Arthur, Tasmania, in 1996. Those ongoing trials using MDMA are sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), an organization led by Rick Doblin that’s worked for 35 years to see such treatments used as a therapy for emotional trauma.

Ball had mentioned during the show that writing on the subject of psychedelics for a high-profile mainstream media outlet like Forbes was having an impact, particularly with people in the 5-MeO-DMT community. I had been covering that topic with greater frequency since early 2020, when a story I wrote about psychoactive toad venom containing 5-MeO-DMT garnered hundreds of thousands of views. 

The Rotary representative, who had heard the podcast the week it aired, emailed me saying: “As the coordinator for the Rotary morning club in Sebastopol, I’ve been looking for a long time for the right person to discuss the post-war-on-drugs psychedelic rethink. It’s a long shot, I know, but I’d like to invite you to spend a half hour with us on a Wednesday morning sometime in the next few months.”

It wasn’t a longshot at all. I fully welcomed the opportunity to give such a talk and was excited to speak to Rotary Club members—as they were not the usual bunch I typically addressed. Over the course of the last year since publishing my booklet, I’ve been invited to speak at psychedelic-focused conferences and symposiums and it began to feel like I was preaching to the choir. Not many people who heard me at those events needed informing on the subject of psychedelics. 

At the Rotary on the other hand, I was bound to be talking to people who knew far less about new psychedelic therapies. Many of them would probably have little knowledge about the likelihood of psychedelic treatments becoming legal, doctor-prescribed options within the next couple of years. I would discover during my talk that one of the Rotary members was an addiction specialist who was particularly interested in hearing how a drug that contained methamphetamine was going to be a useful tool for society.

While Sebastopol is little more than an hour drive outside of San Francisco, not far from the city the landscape transforms to rural, and with it political views skew from liberal to moderate/conservative. I was about a quarter of the way into my talk when I asked if there were any questions. More than a few hands shot up. 

A fair question posed by the addiction specialist concerned the relationship between MDMA and of methamphetamine (the “MA” in 3,4-methyl​enedioxy​methamphetamine). The gentleman had clearly seen his share of people addicted to the street drug crystal meth, which can be a highly addictive substance. Abuse of methamphetamine can lead to paranoia, depression, and hallucinations. How could the FDA knowingly promote a drug therapy that might have such dire consequences for users? 

Like many drugs, there is a risk of addiction when misused. Methamphetamine is a worthwhile compound already used clinically—for instance, in the form of the doctor-prescribed drug Desoxyn—to treat attention-deficit hyperactivity disorder (ADHD). In the case of MDMA-assisted therapy for the treatment of PTSD, the methamphetamine component is beneficial in that it keeps patients alert and engaged during arduous periods of self-reflection that can last for six to eight hours. Whereas the meth abuse described by the addiction specialist is typically recreational use (and illegal), it’s key to note that clinical trials of MDMA occur under rigorous medical settings. 

I explained to the crowd that as the trials sponsored by MAPS continue on their positive trajectory and become legal therapies, commercialized MDMA therapy will certainly require the same rigorous protocols and administration by medical doctors.

Another question that I didn’t expect to hear, but a reasonable one to ask, concerned people driving while under the influence of MDMA. Wasn’t that going to add to the already dismal death toll of impaired-driving accidents? In clinical settings, this simply isn’t advised and should not occur. Much like driving a vehicle after an invasive surgical procedure where something like morphine is prescribed, MDMA-assisted treatments occur in an inpatient setting where patients typically spend the night following treatment sessions. 

The tenor of the next few questions followed that same safety theme. It was clear that nearly everyone there had some understanding of the drug Ecstasy—much of it from their exposure to news about illegal use—but many wrestled with separating the recreationally used drug from the clinically administered medicine. Still, for a group that knew very little about MDMA therapies, all their concerns were rational and thoughtful points. 

The biggest takeaway I had from my talk was the overall interest and enthusiasm most of the people had for learning more about psychedelic therapies. I knew my talk had a real impact when the final questions from the crowd centered around how people can personally participate in these MDMA-assisted therapy clinical trials. It meant that they saw this as a genuine viable option. Opportunities do exist around the world that offer volunteers participation in such clinical studies, as long as they qualify for enrollment criteria based on the goal of the study. There was also interest from one Rotary member to know if clinical research included examination of military personnel with PTSD. A study is currently underway for veterans with combat-related, refractory PTSD, with an estimated study completion date of December 2023.

By the end of my talk the crowd seemed pleased and eager to learn more. I sold a handful of books and was asked if I’d like to speak at other Rotary Clubs in the area. I said I certainly would. Though I’m not paid for such speaking engagements, the opportunity to communicate directly to mainstream America on this topic is something I would never pass up. 

Image: Nicki Adams using adapted photo by Ossewa

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