The Psychedelic Renaissance: Past, Present & Beyond

This will be an official thread where I drop new research, old research and interesting discoveries regarding psychedelics.

But before getting into the science, there’s something fascinating about just how deeply psychedelics seem to be woven into human history.

We have peyote specimens containing mescaline dating back around 5,700 years. Ancient Mesoamerican cultures left behind mushroom imagery and ritual objects. San Pedro appears in Andean ceremonial art thousands of years ago. Somewhere along the way, humans clearly discovered that certain plants could reliably open up radically different states of consciousness…and many cultures treated those states as genuine contact with another layer of reality.

One of my favorite mysteries is ayahuasca. Ayahuasca contains the DMT molecule, which you’ve all heard of at this point from Joe Rogans ramblings and experiences describing entering what feels like hyperspace or the 5th dimension and intelligent entities that interact with you telepathically.

What makes those experiences interesting is that people all throughout the world, would experience the same ‘machine elves’ or ‘greys’ or ‘praying mantis beings’ or ‘jester’ entities… even without hearing about it from others.Keep in mind, DMT is not only found in various plants and animals, but in humans as well. So, anyways…

A classic preparation of ayahuasca combines a DMT-containing plant with a completely different vine containing compounds that prevent the body from immediately destroying the DMT. One provides the psychedelic molecule and the other essentially provides the chemical key that makes it orally active. The odds of being able to find this random and potentially toxic combination to work is extremely low.

Amazonian cultures discovered this relationship long before anyone knew what DMT or enzymes were…and some of their shamans’ traditional explanation for how knowledge like this was acquired is simply that the plants taught them.

Some healers would actually take the psychedelic themselves to diagnose another person’s illness, entering the visionary state to search for its source or receive information about what medicine was needed. Plants could be regarded as teachers, spirits could be consulted, and visions could be treated as sources of knowledge rather than hallucinations to be ignored. And I mean… that’s how they discovered all the healing medicines throughout the jungle without the scientific method.

But now this raises a much bigger historical question. How much have psychedelic experiences influenced humanity’s ideas about gods, spirits and whatever exists beyond ordinary consciousness?

One of the more interesting possibilities is that psychedelics may have helped shape some early religious ideas themselves. Ancient India had Soma, the mysterious sacred drink of the Rig Veda, while ancient Greece had the Eleusinian Mysteries, where initiates drank a secret sacrament before undergoing an experience tied to death, rebirth and the divine.

More broadly, psychedelics are unusually good at producing experiences people describe as direct contact with God, spirits, higher intelligence or some deeper layer of reality. If ancient people were repeatedly having experiences like that, it’s at least conceivable that some visions, deities, myths or even entire religious traditions may have grown out of attempts to interpret and preserve those encounters.

And if you want to go even further out there, Terence McKenna famously proposed that psilocybin mushrooms may have influenced human cognition and culture itself through his “stoned ape” hypothesis that proposes that the evolution of consciousness was accelerated through cavemen dabbling with psychedelics. Very speculative…but an interesting thought when psychedelics have apparently been accompanying humanity for thousands of years.

Whatever the ultimate explanations are, psychedelics clearly didn’t enter human history with hippies in the 1960s.

By the time Western scientists began putting LSD and psilocybin into laboratories, humanity had already been exploring these states for thousands of years.

So… from here on out, I’m going to be listing what all the research in the 50s and 60s was reporting on psychedelics.

I will be using AI to summarize the research and link all of it as well.

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The recent psychedelic “renaissance” is actually a renaissance in the literal sense. Scientists aren’t suddenly studying these substances for the first time.

There was already a massive wave of psychedelic research throughout the 1950s and 60s. More than 1,000 clinical papers were reportedly published during that era, describing psychedelic treatment involving tens of thousands of patients.

A lot of those studies wouldn’t meet the methodological standards we use today, so I wouldn’t take every number below as definitive proof. But some of the results were honestly kind of wild, and several of the questions researchers were asking 60 years ago are basically the same ones being investigated again today.

1960: One of the first large safety surveys looked at nearly 5,000 people across more than 25,000 LSD/mescaline sessions.

Among healthy experimental subjects, there were no reported suicides or suicide attempts, and prolonged psychotic reactions occurred in roughly 0.8 per 1,000 participants.

Rates were somewhat higher among psychiatric patients, which is one reason modern trials screen participants carefully.

Sidney Cohen, Lysergic Acid Diethylamide: Side Effects and Complications (1960). PMID: 13811003.

1960: LSD-assisted psychotherapy was reported in 110 psychiatric patients, many of whom had already undergone previous therapy.

Researchers Chandler and Hartman reported that 50 showed considerable, marked or outstanding improvement, while another 38 showed some degree of improvement.

There wasn’t a randomized control group, so these numbers have to be taken cautiously, but this was one of the early studies that helped generate enormous interest in psychedelic-assisted psychotherapy.

Chandler & Hartman, Lysergic Acid Diethylamide (LSD-25) as a Facilitating Agent in Psychotherapy (1960). DOI: 10.1001/archpsyc.1960.03590090042008.

1961: One of the famous early alcoholism studies treated 61 people with long histories of severe alcohol problems.

At follow-up between 3 and 18 months later, 30 were completely abstinent, another 16 had substantially reduced their drinking, and 15 were unchanged.

So 46 of the 61 showed improvement after treatment.

Again, this was an open-label study rather than a modern randomized trial, but those numbers were obviously enough to get researchers’ attention.

MacLean et al., The Use of LSD-25 in the Treatment of Alcoholism and Other Psychiatric Problems (1961). DOI: 10.15288/qjsa.1961.22.034.

1962: Another LSD alcoholism program followed 33 patients for as long as 88 weeks.

Seven were reported completely abstinent and another ten substantially reduced their drinking. Six were lost to follow-up.

O’Reilly & Reich, Lysergic Acid and the Alcoholic (1962). PMID: 14480914.

1962: The famous “Good Friday Experiment” tested whether psilocybin could reliably produce genuine mystical-type experiences.

Twenty theology students were randomly given either psilocybin or an active placebo during a Good Friday church service.

The psilocybin group scored dramatically higher across measures like unity, sacredness, positive mood and transcendence of time and space. Eight of the ten psilocybin participants experienced at least seven of the nine features researchers associated with mystical experience.

What’s especially interesting is that when researchers tracked most of these people down about 25 years later, the psilocybin group still described substantial positive effects from that single experience.

Walter Pahnke, Good Friday Experiment, 1962/1966; long-term follow-up by Rick Doblin, 1991.

1963: Another alcoholism study compared 70 patients receiving LSD-assisted treatment with 55 receiving conventional individual psychotherapy.

Of the LSD-treated patients, 39 were abstinent and another 7 were drinking substantially less at follow-up.

In the comparison group, 8 were abstinent and 4 had reduced their drinking.

There were major limitations here, particularly the fact that the groups weren’t randomized and many control participants were lost to follow-up. Still, this was one of the early results that made researchers wonder whether a psychedelic experience could interrupt severe addiction.

Jensen & Ramsay, Treatment of Chronic Alcoholism with Lysergic Acid Diethylamide (1963). DOI: 10.1177/070674376300800305.

1963: LSD was even experimented with in people who had repeatedly committed serious crimes.

Dutch psychiatrist G.W. Arendsen-Hein treated 21 men described at the time as severe “criminal psychopaths,” many with histories of 5 to 20 court sentences each.

Following repeated LSD-assisted psychotherapy sessions, 12 were described as clinically improved and another 2 as greatly improved.

This wasn’t a controlled trial and we don’t have reliable recidivism data showing that LSD stopped them from committing crimes, so I wouldn’t make that claim. But the fact that psychiatrists were seeing psychological improvement in people considered almost untreatable at the time is still fascinating.

Arendsen-Hein, LSD in the Treatment of Criminal Psychopaths (1963).

1964: LSD was compared with powerful opioid painkillers in 50 seriously ill patients, most suffering from terminal cancer.

Researchers compared LSD with meperidine and hydromorphone.

LSD produced pain relief that lasted considerably longer than either opioid. Researchers also noticed something unexpected: many patients became noticeably less distressed about dying and were able to discuss death much more freely.

This observation eventually helped inspire the modern research into psychedelics for end-of-life anxiety.

Kast & Collins (1964).

1964: Another follow-up looked at 68 people treated with LSD for chronic alcoholism.

Twenty-six were abstinent during the follow-up period.

Even more interestingly, the type of psychedelic experience appeared to predict the likelihood of abstinence…an early hint of something modern psychedelic studies repeatedly find today: the subjective experience itself may actually be connected to therapeutic outcome.

O’Reilly & Funk, LSD in Chronic Alcoholism (1964). DOI: 10.1177/070674376400900311.

1964: LSD-assisted psychotherapy was studied in another 100 psychiatric patients.

Researchers reported 47 recovered and another 18 improved, compared with substantially poorer outcomes in a historical comparison group treated without LSD.

This wasn’t a randomized modern clinical trial, so again, don’t read “47 recovered” as “LSD cures 47% of people.” But researchers were repeatedly seeing enough improvement to keep investigating.

Whitaker (1964).

1966: Researchers even tested psychedelics for creative problem-solving.

Professionals were brought in with real technical and creative problems they had been unable to solve.

During psychedelic sessions, participants showed significant improvements on some measures of creative thinking and visual problem-solving. They also described less fear of making mistakes, fewer inhibitions and an increased ability to look at problems from unusual perspectives.

Some participants reportedly came away with solutions that were later useful in their actual professional work.

Harman et al., Psychedelic Agents in Creative Problem-Solving: A Pilot Study (1966).

1967: At Spring Grove State Hospital, 69 people with alcoholism underwent psychedelic psychotherapy with LSD.

At six months, roughly one-third remained abstinent, while researchers also reported statistically significant positive changes across most of their clinical measures.

The researchers concluded that psychedelic therapy appeared to add something valuable to existing alcoholism treatment, while emphasizing that it required trained professionals and careful preparation.

Kurland et al., Psychedelic Therapy Utilizing LSD in the Treatment of the Alcoholic Patient (1967). DOI: 10.1176/ajp.123.10.1202.

1969: LSD-assisted psychotherapy was studied in 22 people dying from cancer who were experiencing depression, anxiety and fear of death.

Fourteen of the 22 showed meaningful psychological improvement after treatment, and six of those improvements were described as dramatic.

Researchers reported reductions in depression, anxiety and fear of death along with greater relaxation, better family relationships and greater ability to tolerate pain.

Five of the six people who had especially intense “peak” psychedelic experiences were also among those who improved the most.

Pahnke, Kurland, Goodman & Richards, LSD-Assisted Psychotherapy with Terminal Cancer Patients (1969). PMID: 5348915.

1969: A randomized alcoholism study found an interesting short-term effect even when researchers deliberately removed psychotherapy from the equation.

Seventy-two men received either a single 600 µg dose of LSD or dextroamphetamine.

At two months, the LSD group was doing significantly better.

By six months, however, the difference disappeared.

I actually think results like this are important because they hint at something researchers are still arguing about today: simply giving someone a psychedelic may not be the same thing as creating an environment where the experience can actually be integrated into their life.

Hollister, Shelton & Krieger, A Controlled Comparison of LSD and Dextroamphetamine in Alcoholics (1969). DOI: 10.1176/ajp.125.10.1352.

And here’s probably the most interesting part in hindsight.

Decades later, researchers went back and performed a modern meta-analysis of six randomized LSD trials for alcoholism from this old era, involving 536 people altogether.

When the results were pooled, a single dose of LSD was associated with significantly greater improvement in alcohol misuse than the comparison conditions.

So while a lot of these individual old studies had methodological problems, the alcoholism signal didn’t simply disappear when researchers went back and analyzed the randomized evidence together.

Krebs & Johansen, LSD for Alcoholism: Meta-analysis of Randomized Controlled Trials (2012).

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Psychedelics: What the Last 10 Years of Research Has Been Finding

Over the next while I’m probably going to be posting more about psychedelics, so I figured this would be a good place to start.

A lot of the public perception around psychedelics is still based on ideas from decades ago, while the actual research landscape has changed pretty dramatically. Psilocybin, LSD, DMT, MDMA and related compounds are now being seriously studied for depression, PTSD, addiction, anxiety, neuroplasticity, chronic pain and even the basic mechanisms of how the brain learns and changes.

I’m not posting this to say psychedelics are harmless, that they’re miracle cures, or that everyone should take them. Some of these studies are small, some are observational, and some are animal research that hasn’t yet been demonstrated in humans. Psychedelics can also produce genuinely difficult or harmful experiences in some people.

I just wanted to collect some of the research from roughly the last decade in one place and let it speak for itself. I’ll probably continue adding studies here over time.

Oregon’s legal psilocybin program followed 346 people receiving supervised psilocybin. One month later, 92.2% said they had benefited from the experience. Rates of moderate-to-severe depression, anxiety and PTSD symptoms also fell substantially. Serious behavioral reactions requiring medical attention occurred in about 1.2% of participants.

A single 25 mg dose of psilocybin produced rapid and lasting reductions in major depression in a randomized trial of 104 adults. The benefits were still measurable six weeks later, and there were no serious treatment-related adverse events.

https://jamanetwork.com/journals/jama/fullarticle/2808950

Five years after receiving psilocybin-assisted therapy for major depression, 67% of participants in one small follow-up study were still in remission. Most had received other forms of treatment during those five years as well, so the long-term improvement can’t be attributed to psilocybin alone, but the durability is remarkable.

Psilocybin-assisted therapy significantly reduced heavy drinking in a randomized clinical trial for alcohol use disorder. Researchers have also found changes in brain circuits involved in emotional regulation, craving and goal-directed behavior after treatment.

Psilocybin therapy increased cognitive flexibility in people with major depression. In other words, participants became measurably better at shifting away from rigid patterns of thinking, with improvements still present weeks later.

https://www.nature.com/articles/s41398-021-01706-y

A major Nature study found that several psychedelics can reopen a “critical period” for social learning in adult mice. Critical periods are windows during development when the brain is unusually receptive to learning and change. Different psychedelics kept this window open for different lengths of time.

https://www.nature.com/articles/s41586-023-06204-3

Researchers in Science identified a mechanism through which psychedelics promote neuroplasticity. LSD, psilocin and related compounds can enter neurons and activate serotonin 5-HT2A receptors located inside the cell, triggering pathways involved in neuronal growth and remodeling.

https://www.science.org/doi/10.1126/science.adf0435

A major review in Nature Reviews Neuroscience concluded that psychedelics and ketamine can trigger structural changes in brain cells. Animal research repeatedly shows growth of dendritic spines, the tiny structures neurons use to form connections with each other.

https://www.nature.com/articles/s41583-024-00876-0

Human LSD research found that a 200 µg dose significantly increased blood levels of BDNF. BDNF is an important growth factor involved in neuronal health and plasticity. This doesn’t prove LSD creates entirely new neurons in humans, but it adds to the evidence that psychedelics affect biological systems involved in brain plasticity.

https://www.nature.com/articles/s41386-020-00883-6

Brain imaging studies have found lasting changes in emotional and brain-network processing after psilocybin therapy. In one study of treatment-resistant depression, reduced blood flow in the amygdala after treatment was associated with reduced depression symptoms.

Psilocybin appears to temporarily change the way different parts of the brain communicate. Rather than simply making the brain “more connected,” research suggests some normally separate sensory systems become more integrated while higher-order networks become less rigidly organized.

https://www.pnas.org/content/117/17/9566

A small placebo-controlled study found that a single dose of psilocybin reduced migraine frequency for weeks afterward. The effect appeared to outlast the psychedelic experience itself.

Controlled research in healthy volunteers found 10 mg and 25 mg doses of psilocybin were generally well tolerated, with no persistent negative effects detected in the measures used by the study.

A 2026 phase II trial found that one short DMT session combined with psychological support significantly reduced symptoms of major depression compared with placebo. Improvements appeared within a week and persisted for as long as three months during follow-up.

https://www.nature.com/articles/s41591-025-04154-z

An open-label trial of LSD microdosing in 19 people with major depression reported roughly a 60% reduction in depression scores after eight weeks. Improvements were still present months later. Because there was no placebo group, however, larger controlled trials are needed before knowing how much of the improvement was caused by LSD itself.

https://www.sciencedirect.com/science/article/pii/S0028390825004708

Researchers developed an LSD-inspired compound called JRT that produced strong neuroplastic effects without producing the usual psychedelic-like behavior in mice. It increased dendritic spine density by 46% and synapse density by 18% in the prefrontal cortex and produced antidepressant-like and cognitive effects in animal models.

Another non-hallucinogenic psychedelic-inspired compound produced rapid structural and behavioral effects in animal models of stress. This line of research is especially interesting because scientists are now trying to separate psychedelic neuroplasticity from hallucination itself.

A single dose of DMT given after chronic stress reversed depression-like behavior and cognitive problems in mice. Researchers also found restoration of hippocampal neurogenesis, giving another possible biological mechanism for some psychedelic effects.

https://www.nature.com/articles/s41398-026-03852-7

A single dose of psilocybin produced lasting relief from chronic pain and depression-like behavior in mouse models. The effects lasted well beyond the acute psychedelic period and involved changes in prefrontal brain circuits.

https://www.nature.com/articles/s41593-025-02068-0

Animal research has shown that 5-MeO-DMT can produce long-lasting structural plasticity in the brain.

Research on ayahuasca has found effects on fear learning and fear extinction in animals. This is particularly interesting for researchers studying PTSD and anxiety, although animal findings obviously don’t establish it as a treatment in humans.

Large observational studies of ayahuasca users have reported substantial improvements in depression and anxiety. These studies can’t establish cause and effect the way randomized trials can, but the size of the reported associations has helped drive further research.

MDMA-assisted psychotherapy has been associated with improvements in sleep among people being treated for PTSD.

Studies have also begun looking at what predicts whether someone has a beneficial or difficult psychedelic experience. Traits like openness, acceptance and willingness to surrender to the experience have been associated with better outcomes, while high levels of apprehension or emotional preoccupation may increase the likelihood of challenging experiences.

LSD, psilocybin and mescaline may be more phenomenologically similar than people assume. In a controlled comparison, researchers found no clear qualitative differences between the altered states produced by 100 µg LSD, 20 mg psilocybin and 500 mg mescaline, although their duration and pharmacology differed.

Research has even compared psychedelic experiences with near-death experiences. DMT produced experiences with significant phenomenological overlap with reports of near-death experiences, giving researchers another way to study extraordinary states of consciousness.

And one of the stranger recent findings: researchers repeatedly scanned a woman who can voluntarily enter an intense visionary state without taking any drugs. Across 20 fMRI sessions, her brain networks reliably reorganized as she entered a state involving vivid geometric imagery, diminished body boundaries, serenity and a strong feeling of unity.

That last one obviously isn’t evidence for psychedelic therapy…I just think it’s incredibly cool when viewed alongside the rest of this research. It suggests that at least some features we associate with “psychedelic consciousness” may be states the human brain is capable of generating on its own.

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If people still read books, then The Way of the Psychonaut by Stanislav Grof is a great read..

The first volume is a summary of the history and traditional and therapeutic use of psychedelics, the second one focuses a bit more on his specific research/work.

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