Archive for the ‘Psilocybin’ Category


Synthetic psilocybin, a compound found in magic mushrooms, has been administered to cancer patients in a study at New York University. Researcher Anthony Bossis says many subjects report decreased depression and fear of death after their session. Although some patients do not report persistent positive feelings, none report persistent adverse effects. Photo: Bossis, NYU.

By John Horgan

Bossis, a psychologist at New York University, belongs to an intrepid cadre of scientists reviving research into psychedelics’ therapeutic potential. I say “reviving” because research on psychedelics thrived in the 1950s and 1960s before being crushed by a wave of anti-psychedelic hostility and legislation.

Psychedelics such as LSD, psilocybin and mescaline are still illegal in the U.S. But over the past two decades, researchers have gradually gained permission from federal and other authorities to carry out experiments with the drugs. Together with physicians Stephen Ross and Jeffrey Guss, Bossis has tested the potential of psilocybin—the primary active ingredient of “magic mushrooms”–to alleviate anxiety and depression in cancer patients.

Journalist Michael Pollan described the work of Bossis and others in The New Yorker last year. Pollan said researchers at NYU and Johns Hopkins had overseen 500 psilocybin sessions and observed “no serious adverse effects.” Many subjects underwent mystical experiences, which consist of “feelings of unity, sacredness, ineffability, peace and joy,” as well as the conviction that you have discovered “an objective truth about reality.”

Pollan’s report was so upbeat that I felt obliged to push back a bit, pointing out that not all psychedelic experiences—or mystical ones–are consoling. In The Varieties of Religious Experience, William James emphasized that some mystics have “melancholic” or “diabolical” visions, in which ultimate reality appears terrifyingly alien and uncaring.

Taking psychedelics in a supervised research setting doesn’t entirely eliminate the risk of a bad trip. That lesson emerged from a study in the early 1990s by psychiatrist Rick Strassman, who injected dimethyltryptamine, DMT, into human volunteers.

From 1990 to 1995, Strassman supervised more than 400 DMT sessions involving 60 subjects. Many reported dissolving blissfully into a radiant light or sensing the presence of a loving god. But 25 subjects had “adverse effects,” including terrifying hallucinations of “aliens” that took the shape of robots, insects or reptiles. (For more on Strassman’s study, see this link: https://www.rickstrassman.com/index.php?option=com_content&view=article&id=61&Itemid=60

Swiss chemist Albert Hofmann, who discovered LSD’s powers in 1943 and later synthesized psilocybin, sometimes expressed misgivings about psychedelics. When I interviewed him in 1999, he said psychedelics have enormous scientific, therapeutic and spiritual potential. He hoped someday people would take psychedelics in “meditation centers” to awaken their religious awe.

Yet in his 1980 memoir LSD: My Problem Child, Hofmann confessed that he occasionally regretted his role in popularizing psychedelics, which he feared represent “a forbidden transgression of limits.” He compared his discoveries to nuclear fission; just as fission threatens our fundamental physical integrity, so do psychedelics “attack the spiritual center of the personality, the self.”

I had these concerns in mind when I attended a recent talk by Bossis near New York University. A large, bearded man who exudes warmth and enthusiasm, Bossis couldn’t reveal details of the cancer-patient study, a paper on which is under review, but he made it clear that the results were positive.

Many subjects reported decreased depression and fear of death and “improved well-being” after their session. Some called the experience among the best of their lives, with spiritual implications. An atheist woman described feeling “bathed in God’s love.”

Bossis said psychedelic therapy could transform the way people die, making the experience much more meaningful. He quoted philosopher Victor Frankl, who said, “Man is not destroyed by suffering. He is destroyed by suffering without meaning.”

During the Q&A, I asked Bossis about bad trips. Wouldn’t it be awful, I suggested, if a dying patient’s last significant experience was negative? Bossis said he and his co-researchers were acutely aware of that risk. They minimized adverse reactions by managing the set (i.e., mindset, or expectations, of the subject) and setting (context of the session).

First, they screen patients for mental illness, eliminating those with, say, a family history of schizophrenia. Second, the researchers prepare patients for sessions, telling them to expect and explore rather than suppressing negative emotions, such as fear or grief. Third, the sessions take place in a safe, comfortable room, which patients can decorate with personal items, such as photographs or works of art. A researcher is present during sessions but avoids verbal interactions that might distract the patient from her inner journey. Patients and researchers generally talk about sessions the following day.

These methods seem to work. Some patients, to be sure, became frightened or melancholy. One dwelled on the horrors of the Holocaust, which had killed many members of his family, but he found the experience meaningful. Some patients did not emerge from their sessions with persistent positive feelings, Bossis said, but none reported persistent adverse effects.

Bossis has begun a new study that involves giving psilocybin to religious leaders, such as priests and rabbis. His hope is that these subjects will gain a deeper understanding of the mystical roots of their faiths.

http://blogs.scientificamerican.com/cross-check/psychedelic-therapy-and-bad-trips/

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lsd

by Angus Chen

Some users of LSD say one of the most profound parts of the experience is a deep oneness with the universe. The hallucinogenic drug might be causing this by blurring boundaries in the brain, too.

The sensation that the boundaries between yourself and the world around you are erasing correlates to changes in brain connectivity while on LSD, according to a study published Wednesday in Current Biology. Scientists gave 15 volunteers either a drop of acid or a placebo and slid them into an MRI scanner to monitor brain activity.

After about an hour, when the high begins peaking, the brains of people on acid looked markedly different than those on the placebo. For those on LSD, activity in certain areas of their brain, particularly areas rich in neurons associated with serotonin, ramped up.

Their sensory cortices, which process sensations like sight and touch, became far more connected than usual to the frontal parietal network, which is involved with our sense of self. “The stronger that communication, the stronger the experience of the dissolution [of self],” says Enzo Tagliazucchi, the lead author and a researcher at the Netherlands Institute for Neuroscience.

Tagliazucchi speculates that what’s happening is a confusion of information. Your brain on acid, flooded with signals crisscrossing between these regions, begins muddling the things you see, feel, taste or hear around you with you. This can create the perception that you and, say, the pizza you’re eating are no longer separate entities. You are the pizza and the world beyond the windowsill. You are the church and the tree and the hill.

Albert Hofmann, the discoverer of LSD, described this in his book LSD: My Problem Child. “A portion of the self overflows into the outer world, into objects, which begin to live, to have another, a deeper meaning,” he wrote. He felt the world would be a better place if more people understood this. “What is needed today is a fundamental re-experience of the oneness of all living things.”

The sensation is neurologically similar to synesthesia, Tagliazucchi thinks. “In synesthesia, you mix up sensory modalities. You can feel the color of a sound or smell the sound. This happens in LSD, too,” Tagliazucchi says. “And ego dissolution is a form of synesthesia, but it’s a synesthesia of areas of brain with consciousness of self and the external environment. You lose track of which is which.”

Tagliazucchi and other researchers also measured the volunteers’ brain electrical activity with another device. Our brains normally generate a regular rhythm of electrical activity called the alpha rhythm, which links to our brain’s ability to suppress irrelevant activity. But in a different paper published on Monday in the Proceedings of the National Academy of Sciences, he and several co-authors show that LSD weakens the alpha rhythm. He thinks this weakening could make the hallucinations seem more real.

The idea is intriguing if still somewhat speculative, says Dr. Charles Grob, a psychiatrist at the Harbor-UCLA Medical Center who was not involved with the work. “They may genuinely be on to something. This should really further our understanding of the brain and consciousness.” And, he says, the work highlights hallucinogens’ powerful therapeutic potential.

The altered state of reality that comes with psychedelics might enhance psychotherapy, Grob thinks. “Hallucinogens are a catalyst,” he says. “In well-prepared subjects, you might elicit powerful, altered states of consciousness. [That] has been predicative of positive therapeutic outcomes.”

In recent years, psychedelics have been trickling their way back to psychiatric research. LSD was considered a good candidate for psychiatric treatment until 1966, when it was outlawed and became very difficult to obtain for study. Grob has done work testing the treatment potential of psilocybin, the active compound in hallucinogenic mushrooms.

He imagines a future where psychedelics are commonly used to treat a range of conditions. “[There could] be a peaceful room attractively fixed up with nice paintings, objects to look at, fresh flowers, a chair or recliner for the patient and two therapists in the room,” he muses. “A safe container for that individual as they explore deep inner space, inner terrain.”

Grob believes the right candidate would benefit greatly from LSD or other hallucinogen therapy, though he cautions that bad experiences can still happen for some on the drugs. Those who are at risk for schizophrenia may want to avoid psychedelics, Tagliazucchi says. “There has been evidence saying what could happen is LSD could trigger the disease and turn it into full-fledged schizophrenia,” he says. “There is a lot of debate around this. It’s an open topic.”

Tagliazucchi thinks that this particular ability of psychedelics to evoke a sense of dissolution of self and unity with the external environment has already helped some patients. “Psilocybin has been used to treat anxiety with terminal cancer patients,” he says. “One reason why they felt so good after treatment is the ego dissolution is they become part of something larger: the universe. This led them to a new perspective on their death.”

http://www.npr.org/sections/health-shots/2016/04/13/474071268/how-lsd-makes-your-brain-one-with-the-universe

by Natalie Wolchover

The main theory of psychedelics, first fleshed out by a Swiss researcher named Franz Vollenweider, is that drugs like LSD and psilocybin, the active ingredient in “magic” mushrooms, tune down the thalamus’ activity. Essentially, the thalamus on a psychedelic drug lets unprocessed information through to consciousness, like a bad email spam filter. “Colors become brighter , people see things they never noticed before and make associations that they never made before,” Sewell said.

LSD, or acid, and its mind-bending effects have been made famous by pop culture hits like “Fear and Loathing in Las Vegas,” a film about the psychedelic escapades of writer Hunter S. Thompson. Oversaturated colors, swirling walls and intense emotions all supposedly come into play when you’re tripping. But how does acid make people trip?

Life’s Little Mysteries asked Andrew Sewell, a Yale psychiatrist and one of the few U.S.-based psychedelic drug researchers, to explain why LSD short for lysergic acid diethylamide does what it does to the brain.

His explanation begins with a brief rundown of how the brain processes information under normal circumstances. It all starts in the thalamus, a node perched on top of the brain stem, right smack dab in the middle of the brain. “Most sensory impressions are routed through the thalamus, which acts as a gatekeeper, determining what’s relevant and what isn’t and deciding where the signals should go,” Sewell said.

“Consequently, your perception of the world is governed by a combination of ‘bottom-up’ processing, starting … with incoming signals, combined with ‘top-down’ processing, in which selective filters are applied by your brain to cut down the overwhelming amount of information to a more manageable and relevant subset that you can then make decisions about.

“In other words, people tend to see what they’ve been trained to see, and hear what they’ve been trained to hear.”

The main theory of psychedelics, first fleshed out by a Swiss researcher named Franz Vollenweider, is that drugs like LSD and psilocybin, the active ingredient in “magic” mushrooms, tune down the thalamus’ activity. Essentially, the thalamus on a psychedelic drug lets unprocessed information through to consciousness, like a bad email spam filter. “Colors become brighter , people see things they never noticed before and make associations that they never made before,” Sewell said.

n a recent paper advocating the revival of psychedelic drug research, psychiatrist Ben Sessa of the University of Bristol in England explained the benefits that psychedelics lend to creativity. “A particular feature of the experience is … a general increase in complexity and openness, such that the usual ego-bound restraints that allow humans to accept given pre-conceived ideas about themselves and the world around them are necessarily challenged. Another important feature is the tendency for users to assign unique and novel meanings to their experience together with an appreciation that they are part of a bigger, universal cosmic oneness.”

But according to Sewell, these unique feelings and experiences come at a price: “disorganization, and an increased likelihood of being overwhelmed.” At least until the drugs wear off, and then you’re left just trying to make sense of it all.

http://www.livescience.com/33167-how-acid-lsd-make-people-trip.html?li_source=pm&li_medium=most-popular&li_campaign=related_test

An analysis of data provided by 135,000 randomly selected participants – including 19,000 people who had used drugs such as LSD and magic mushrooms – finds that use of psychedelics does not increase risk of developing mental health problems. The results are published in the Journal of Psychopharmacology.

Previously, the researchers behind the study – from the Norwegian University of Science and Technology in Trondheim – had conducted a population study investigating associations between mental health and psychedelic use. However, that study, which looked at data from 2001-04, was unable to find a link between use of these drugs and mental health problems.

“Over 30 million US adults have tried psychedelics and there just is not much evidence of health problems,” says author and clinical psychologist Pål-Ørjan Johansen.

“Drug experts consistently rank LSD and psilocybin mushrooms as much less harmful to the individual user and to society compared to alcohol and other controlled substances,” concurs co-author and neuroscientist Teri Krebs.

For their study, they analyzed a data set from the US National Health Survey (2008-2011) consisting of 135,095 randomly selected adults from the US, including 19,299 users of psychedelic drugs.

Krebs and Johansen report that they found no evidence for a link between use of psychedelic drugs and psychological distress, depression, anxiety or suicidal thoughts, plans and attempts.

In fact, on a number of factors, the study found a correlation between use of psychedelic drugs and decreased risk for mental health problems.

“Many people report deeply meaningful experiences and lasting beneficial effects from using psychedelics,” says Krebs.

However, Johansen acknowledges that – given the design of the study – the researchers cannot “exclude the possibility that use of psychedelics might have a negative effect on mental health for some individuals or groups, perhaps counterbalanced at a population level by a positive effect on mental health in others.”

Despite this, Johansen believes that the findings of the study are robust enough to draw the conclusion that prohibition of psychedelic drugs cannot be justified as a public health measure.

Krebs says:

“Concerns have been raised that the ban on use of psychedelics is a violation of the human rights to belief and spiritual practice, full development of the personality, and free-time and play.”

Commenting on the research in a piece for the journal Nature, Charles Grob, a paediatric psychiatrist at the University of California-Los Angeles, says the study “assures us that there were not widespread ‘acid casualties’ in the 1960s.” However, he urges caution when interpreting the results, as individual cases of adverse effects can and do occur as a consequence of psychedelic use.

For instance, Grob describes hallucinogen persisting perception disorder, sometimes referred to as “a never-ending trip.” Patients with this disorder experience “incessant distortions” in their vision, such as shimmering lights and colored dots. “I’ve seen a number of people with these symptoms following a psychedelic experience, and it can be a very serious condition,” says Grob.

http://www.medicalnewstoday.com/articles/290461.php

Humans have been ingesting mind-altering substances for a very long time. Hallucinogen-huffing bowls 2,500 years old (http://www.livescience.com/5240-ancient-family-heirlooms-snort-hallucinogens.html) have been found on islands in the Lesser Antilles, and traditional cultures from the Americas to Africa use hallucinogenic substances for spiritual purposes. Here are some notable substances that send the mind tripping.

LSD is commonly known as “acid,” but its scientific name is a mouthful: lysergic acid diethylamaide. The drug was first synthesized in 1938 from a chemical called ergotamine. Ergotamine, in turn, is produced by a grain fungus that grow on rye.

LSD was originally produced by a pharmaceutical company under the name Delysid, but it got a bad reputation in the 1950s when the CIA decided to research its effects on mind control. The test subjects of the CIA project MKULTRA proved very difficult to control indeed, and many, like counter-culture writer Ken Kesey, started taking the drug for fun (and for their own form of 1960s enlightenment).

ayahuasca-vine-110929

Ayahuasca is a hallucinatory mixture of Amazonian infusions centered around the Banisteriopsis caapi vine. The brew has long been used by native South American tribes for spiritual rituals and healing, and like other hallucinogens, ayahuasca often triggers very intense emotional experiences (vomiting is also common). In 2006, National Geographic writer Kira Salak described her experience with ayahuasca in Peru for the magazine.

” I will never forget what it was like. The overwhelming misery. The certainty of never-ending suffering. No one to help you, no way to escape. Everywhere I looked: darkness so thick that the idea of light seemed inconceivable,” Salak wrote. “Suddenly, I swirled down a tunnel of fire, wailing figures calling out to me in agony, begging me to save them. Others tried to terrorize me. ‘You will never leave here,’ they said. ‘Never. Never.'”

Nonetheless, Salak wrote, when she broke free of her hallucinations, her crippling depression was alleviated. It’s anecdotal experiences like this that have led researchers to investigate the uses of hallucinogens as therapy for mental disorders such as anxiety, depression and post-traumatic stress disorder.

Peyote is a cactus that gets its hallucinatory power from mescaline. Like most hallucinogens, mescaline binds to serotonin receptors in the brain, producing heightened sensations and kaleidoscopic visions.

Native groups in Mexico have used peyote in ceremonies for thousands of years, and other mescaline-producing cacti have long been used by South American tribes for their rituals. Peyote has been the subject of many a court battle because of its role in religious practice; currently, Arizona, Colorado, New Mexico, Nevada and Oregon allow some peyote possession, but only if linked to religious ceremonies, according to Arizona’s Peyote Way Church of God.

The “magic” ingredient in hallucinogenic mushrooms is psilocybin, a compound that breaks down into psilocin in the body. Psilocin bonds to serotonin receptors all over the brain, and can cause hallucinations as well as synesthesia, or the mixture of two senses. Under the influence, for example, a person might feel that they can smell colors.

In keeping with the human tradition of eating anything that might alter your mind, people have been ingesting psilocybin-continuing mushrooms for thousands of years. Synthetic psilocybin is now under study as a potential treatment for anxiety, depression and addiction.

Best known by its street name, “angel dust,” PCP stands for phencyclidine. The drug blocks receptors in the brain for the neurotransmitter glutamate. It’s more dangerous than other hallucinogens, with schizophrenia-like symptoms and nasty side effects.

Those side effects are why PCP has no medical uses. The drug was tested as an anesthetic in the 1950s and used briefly to knock out animals during veterinary surgeries. But by the 1960s, PCP had hit the streets and was being used as a recreation drug, famous for the feelings of euphoria and invincibility it bestowed on the user. Unfortunately, a side effect of all that euphoria is sometimes truly destructive behavior, including users trying to jump out of windows or otherwise self-mutilating. Not to mention that high enough doses can cause convulsions.

Derived from the African iboga plant, ibogaine is another hallucinogen with a long history of tribal use. More recently, the drug has shown promise in treating addiction, although mostly in Mexico and Europe where ibogaine treatment is not prohibited as it is in the U.S.

Using ibogaine as therapy is tricky, however. The drug can cause heart rhythm problems, and vomiting is a common side effect. The Massachusetts-based Multidisciplinary Association for Psychedelic Research (MAPS) reports that an estimated 1 in 300 ibogaine users die due to the drug. The group is studying the long-term effects of ibogaine on patients in drug treatment programs in New Zealand and Mexico.

Salvia divinorum, also known as seer’s or diviner’s sage, grows in the cloud forest of Oaxaca, Mexico. The native Mazatec people have long used tea made out of the leaves in spiritual ceremonies, but the plant can also be smoked or chewed for its hallucinogenic effects.

Salvia is not currently a controlled substance, according to the National Institute on Drug Abuse, but it is under consideration to be made illegal and placed in the same drug class as marijuana.

Ecstasy, “E” or “X” are the street names for MDMA, or (get ready for a long one) 3,4-methylenedioxymethamphetamine. The drug acts on serotonin in the brain, causing feelings of euphoria, energy and distortions of perception. It can also nudge body temperatures up, raising the risk of heat stroke. Animal studies suggest that MDMA causes long-term and potentially dangerous changes in the brain, according to the National Institute on Drug Abuse.

MDMA was first synthesized by a chemist looking for substances to stop bleeding in 1912. No one paid the compound much mind for the next half-decade, but by the 1970s, MDMA had hit the streets. It was popular at raves and nightclubs and among those who liked their music psychedelic. Today, ecstasy is still a common street drug, but researchers are investigating whether MDMA could be used to treat post-traumatic stress disorder and cancer-related anxiety.

http://www.livescience.com/16286-hallucinogens-lsd-mushrooms-ecstasy-history.html

war_on_drugs_thumb

The decades-long global war on drugs has failed and it’s time to shift the focus from mass incarceration to public health and human rights, according to a new report endorsed by five Nobel Prize-winning economists.

The report, titled “Ending the Drug Wars” and put together by the London School of Economics’ IDEAS center, looks at the high costs and unintended consequences of drug prohibitions on public health and safety, national security and law enforcement.

“The pursuit of a militarized and enforcement-led global ‘war on drugs’ strategy has produced enormous negative outcomes and collateral damage,” says the 82-page report. “These include mass incarceration in the US, highly repressive policies in Asia, vast corruption and political destabilization in Afghanistan and West Africa, immense violence in Latin America, an HIV epidemic in Russia, an acute global shortage of pain medication and the propagation of systematic human rights abuses around the world.”

The report urges the world’s governments to reframe their drug policies around treatment and harm reduction rather than prosecution and prison.

It is also aimed at the United Nations General Assembly, which is preparing to convene a special session on drug policy in 2016. The hope is to push the U.N. to encourage countries to develop their own policies, because the report declares the current one-size-fits-all approach has not proved to be effective.

“The UN must recognize its role is to assist states as they pursue best-practice policies based on scientific evidence, not undermine or counteract them,” said Danny Quah, a professor of economics at LSE and a contributor to the report. “If this alignment occurs, a new and effective international regime can emerge that effectively tackles the global drug problem.”

In addition to contributions from Quah and a dozen other foreign and drug policy experts, the report has been endorsed by five past winners of the Nobel Prize in Economics: Kenneth Arrow (1972), Sir Christopher Pissarides (2010), Thomas Schelling (2005), Vernon Smith (2002) and Oliver Williamson (2009). Also signing on to the report’s foreword are a number of current and former international leaders, including George Shultz, secretary of state under President Ronald Reagan; Nick Clegg, British deputy prime minister; and Javier Solana, the former EU high representative for common foreign and security policy.

Guatemalan President Otto Perez Molina, who has announced that his government may present a plan to legalize production of marijuana and opium poppies by the end of 2014, has also publicly backed the report. Molina plans to discuss the report at the U.N.

A recent Pew survey suggests that Americans may be ready to refocus the U.S. end of the drug war, with 67 percent favoring policies that would provide drug treatment.

“The drug war’s failure has been recognized by public health professionals, security experts, human rights authorities and now some of the world’s most respected economists,” said John Collins, the International Drug Policy Project coordinator at LSE IDEAS. “Leaders need to recognize that toeing the line on current drug control strategies comes with extraordinary human and financial costs to their citizens and economies.”

http://www.huffingtonpost.com/2014/05/06/end-drug-war_n_5275078.html?utm_hp_ref=politics

Thanks to Dr. Lutter for bringing this to the attention of the It’s Interesting community.

drugs

dr nutt
Nutt says politicians often have a “primitive, childish” way of thinking about drugs.

David Nutt is trying to develop a new recreational drug that he hopes will be taken up by millions of people around the world. No, the 62-year-old scientist isn’t “breaking bad.” In fact, he hopes to do good. His drug would be a substitute for alcohol, to create drinks that are just as intoxicating as beer or whiskey but less toxic. And it would come with an antidote to reverse its effects, allowing people to sober up instantly and drive home safely.

Nutt, a neuropsychopharmacologist at Imperial College London and a former top adviser to the British government on drug policy, says he has already identified a couple of candidates, which he is eager to develop further. “We know people like alcohol, they like the relaxation, they like the sense of inebriation,” Nutt says. “Why don’t we just allow them to do it with a drug that isn’t going to rot their liver or their heart?”

But when he presented the idea on a BBC radio program late last year and made an appeal for funding, many were appalled. A charity working on alcohol issues criticized him for “swapping potentially one addictive substance for another”; a commentator called the broadcast “outrageous.” News-papers likened his synthetic drug to soma, the intoxicating compound in Aldous Huxley’s dystopian novel Brave New World. Some of his colleagues dismissed the idea as scientifically unfeasible.

Nutt wasn’t surprised. As a fierce advocate of what he says are more enlightened, rational drug policies, he has been a lightning rod for a long time. Politicians, in Nutt’s view, make irrational decisions about drugs that help them win votes but cost society dearly. Drug policy is often based on the moral judgment that people should not use drugs, he says. Instead, it should reflect what science knows about the harms of different drugs—notably that many are far less harmful than legal substances such as alcohol, he says. The plan for a synthetic alcohol alternative is his own attempt to reduce the damage that drug use can wreak; he believes it could save millions of lives and billions of dollars.

Such views—and the combative way in which he espouses them—frequently land Nutt in fierce disputes. Newspaper commentators have called him “Professor Nutty” or “the dangerous professor.” In 2009, he was sacked from his position as chair of the United Kingdom’s Advisory Council on the Misuse of Drugs, tasked with giving scientific advice to the home secretary, after he criticized a government decision on cannabis.

But in November 2013, he received the John Maddox Prize for standing up for science. “In circumstances that would have humiliated and silenced most people,” wrote neurobiologist Colin Blakemore, one of the judges, “David Nutt continued to affirm the importance of evidence in understanding the harms of drugs and in developing drug policy.”

Controversial comparisons
David Nutt does not look like a dangerous professor. Short and heavyset, he has a jovial, round face and an old-fashioned mustache; one could mistake him for a London taxi driver. He limps slightly, has a down-to-earth way of speaking, and laughs a lot when he talks. “He is a real personality,” says psychopharmacologist Rainer Spanagel of Heidelberg University in Germany. “You can be in a meeting and almost have a result, then he will come in an hour late, stir everything up, and in the end convince everyone of his position.”

Nutt says he realized at an early age that “understanding how the brain works is the most interesting and challenging question in the universe.” When he was a teenager, his father told him a story of how Albert Hofmann, the discoverer of LSD, took a dose of that drug and felt that the bike ride home took hours instead of minutes. “Isn’t that incredible, that a drug can change time?” he asks. On his first night as an undergraduate in Cambridge, he witnessed the powers of drugs again when he went drinking with fellow students. Two of them couldn’t stop. “I just watched them transform themselves. One of them started wailing and crying and the other became incredibly hostile.”

During his clinical training, Nutt says he treated many alcoholics but failed “to get anyone interested in how to reduce their addiction to the drug that was harming them.” He set out to answer that question, first in the United Kingdom, later as the chief of the Section of Clinical Science at the U.S. National Institute on Alcohol Abuse and Alcoholism, a job he held for 2 years. Today, he runs the department of neuropsychopharmacology at Imperial College, using modern imaging techniques to see what happens in the brain when people take drugs or develop an addiction.

But his biggest contribution to science, he says, was a discovery he made quite early in his career: that some molecules don’t just block receptors in the brain, but actually have the opposite effect of the molecules that normally stimulate them—and in doing so shut down a brain pathway. Nutt called these molecules contragonists, and he has made a second career out of being a bit of a contragonist himself, trying to calm society’s overexcited responses to the steady stream of alarming news about drugs.

Fictional affliction
In 2009, Nutt published an article in the Journal of Psychopharmacology comparing the harms from ecstasy with those caused by horse riding. Every 10,000th ecstasy pill is likely to hurt someone, he calculated, while an average horse enthusiast can expect a serious accident every 350 hours of riding. The sport, he concluded, was more dangerous than the notorious party drug. That “raises the critical question of why society tolerates—indeed encourages—certain forms of potentially harmful behaviour but not others such as drug use,” he added.

Politicians were not amused, and Nutt’s whimsical reference to a fictional affliction he called equine addiction syndrome, or “equasy,” did not help. In his book Drugs – Without the Hot Air, Nutt provided his account of a phone conversation he had with U.K. Home Secretary Jacqui Smith after the paper was published. (Smith calls it an “embroidered version” of their talk.)

Smith: “You can’t compare harms from a legal activity with an illegal one.”

Nutt: “Why not?”

“Because one’s illegal.”

“Why is it illegal?”

“Because it’s harmful.”

“Don’t we need to compare harms to determine if it should be illegal?”

“You can’t compare harms from a legal activity with an illegal one.”

Nutt says this kind of circular logic crops up again and again when he discusses recreational drugs with politicians. “It’s what we would call ‘splitting’ in psychiatric terms: this primitive, childish way of thinking things are either good or bad,” he says.

He’s often that outspoken. He likens the way drug laws are hampering legitimate scientific research, for instance into medical applications for psychedelic compounds, to the church’s actions against Galileo and Copernicus. When the United Kingdom recently banned khat, a plant containing a stimulant that’s popular among people from the Horn of Africa and the Arabian Peninsula, he compared the decision with banning cats. And he accuses the Russian government of deliberately using alcohol to weaken the opposition. “However miserable they are, however much they hate their government and their country, they will just drink until they kill themselves, so they won’t protest,” he says.

But it’s his stance on cannabis that got him sacked. In early 2009, ignoring advice from Nutt’s advisory council, Smith upgraded cannabis from class C to class B, increasing the maximum penalty for possession from 2 to 5 years in prison. A few months later, Nutt criticized the decision in a public lecture, arguing that “overall, cannabis use does not lead to major health problems” and that tobacco and alcohol were more harmful. When media reported the remarks, Alan Johnson, who succeeded Smith as home secretary in mid-2009, asked him to resign. “He was asked to go because he cannot be both a government adviser and a campaigner against government policy,” Johnson wrote in a letter in The Guardian.

Nutt did not go quietly. With financial help from a young hedge fund manager, Toby Jackson, he set up a rival body, the Independent Scientific Committee on Drugs, “to ensure that the public can access clear, evidence based information on drugs without interference from political or commercial interest.” Politics have skewed not just drug laws but research itself, he argues. “If you want to get money from the U.S. government to work on a drug, you have to prove it damages the brain,” he says.

One of his favorite examples is a paper that Science published in September 2002. The study, led by George Ricaurte at Johns Hopkins University, seemed to show that monkeys given just two or three doses of ecstasy, chemically known as MDMA, developed severe brain damage. The finding suggested that “even individuals who use MDMA on one occasion may be at risk for substantial brain injury,” the authors wrote. The paper received massive media attention, but it was retracted a year later after the authors discovered that they had accidentally injected the animals not with MDMA but with methamphetamine, also known as crystal meth, which was already known to have the effects seen in the monkeys. Nutt says the mistake should have been obvious from the start because the data were “clearly wrong” and “scientifically implausible.” “If that result was true, then kids would have been dropping dead from Parkinson’s,” he says.

Some resent this combative style. “He is a polarizing figure and the drug policy area is polarized enough,” says Jonathan Caulkins, a professor of public policy at Carnegie Mellon University in Pittsburgh, Pennsylvania. But Jürgen Rehm, an epidemiologist at the Centre for Addiction and Mental Health in Toronto, Canada, says Nutt has helped stimulate debates that were long overdue. “You don’t get to be on the front page of The Lancet and The New York Times unless you sharpen your arguments a little bit,” Rehm says. “I can live with that.”

Ranking the drugs
In 2010, Nutt sparked a new firestorm when he published another comparison: a Lancet paper ranking drugs according to the harm they cause. Nutt and other experts scored a long list of drugs on 16 criteria, nine related to the user, such as death from an overdose or wrecked relationships, and seven related to society, such as drug-fueled violence and economic costs. In the end, every drug was given a score between 0 and 100 to indicate its overall harm. Alcohol came out on top, ahead of heroin; mushrooms and ecstasy were at the low end.

Critics said the study’s methodology was flawed because it didn’t address drug interactions and the social context of drug use. “For instance, the number of fatalities caused by excessive alcohol use is going to depend in part on gun control laws,” says Caulkins, who calls the whole idea of expressing drug harm as a single number “embarrassing.”

Caulkins adds that even if a perfect ranking of drug harms were possible, it wouldn’t mean that politicians should put the tightest control measures on the most harmful drugs. Suppose drug A is more harmful to the individual and society than drug B, he says, but impurities in drug A, when illegally produced, can lead to potentially fatal organ failure while they just taste bad in drug B. If you were going to prohibit only one of the two drugs, it should be drug B, he says, even though it causes less harm per se, because criminalizing drug A would lead to a more dangerous product and more deaths. Nutt’s ranking of drugs, he says, is “a pseudoscientific exercise which is trying to take control of the policy process from a technocratic perspective in a way that isn’t even sound.”

Other scientists defended the paper. Using Nutt’s harm scales, “flawed and limited as they may be, would constitute a quantum leap of progress towards evidence-based and more rational drug policy in Canada and elsewhere,” two Canadian drug scientists wrote in Addiction. Regardless of its quality, the paper has been hugely influential, Rehm says. “Everyone in the E.U. knows that paper, whether they like it or not. There is a time before that paper and a time after it appeared.”

Nutt says his comparisons are an essential first step on the way to more evidence-based drug policies that seek to reduce harm rather than to moralize. The best option would be a regulated market for alcohol and all substances less harmful to the user than alcohol, he argues.

That scenario, under which only heroin, crack cocaine, and methamphetamine would remain illegal, seems unlikely to become a reality. But Nutt says he can already see more rational policies taking hold. Recently, Uruguay and the U.S. states of Colorado and Washington legalized the sale of recreational cannabis, going a step further than the Netherlands, which stopped enforcing laws on the sale and possession of small amounts of soft drugs decades ago. Nutt was also happy to read President Barack Obama’s recent comment that cannabis is less harmful than alcohol. “At last, a politician telling the truth,” he says. “I’ll warn him though—I was sacked for saying that.”

New Zealand, meanwhile, passed a law in 2013 that paves the way for newly invented recreational drugs to be sold legally if they have a “low risk” of harming the user. Nutt, who has advised the New Zealand government, is delighted by what he calls a “rational revolution in dealing with recreational drugs.” The main problem now, he says, is establishing new drugs’ risks—which is difficult because New Zealand does not allow them to be tested on animals—and deciding what “low risk” actually means. “I told them the threshold should be if it is safer than alcohol,” he says. “They said: ‘Oh my god, that is going to be far too dangerous.'”

Safer substitute
Nutt agrees that alcohol is now one of the most dangerous drugs on the market—which is why he’s trying to invent a safer substitute. The World Health Organization estimates that alcohol—whose harms range from liver cirrhosis, cancer, and fetal alcohol syndrome to drunk driving and domestic violence—kills about 2.5 million people annually. “When I scan the brains of people with chronic alcohol dependence, many have brains which are more damaged than those of people with Alzheimer’s,” Nutt says.

In a paper published this month in the Journal of Psychopharmacology, Nutt and Rehm summarize the top six interventions that governments should consider to reduce the harms of alcohol, such as minimum prices and restrictions on the places that can sell hard liquor. They also argue that governments should support the development of alternatives. Nutt points to e-cigarettes—devices that heat and vaporize a nicotine solution—as a model. “In theory, electronic cigarettes could save 5 million lives a year. That is more than [the death toll from] AIDS, malaria, tuberculosis, and meningitis put together,” he says. “I would argue that the e-cigarette is going to be the greatest health invention since vaccination.”

Can an alcohol alternative do the same? “I think that idea is utopian,” says Spanagel, the German psychopharmacologist. One reason is that researchers have recently developed a much more complex picture of what ethanol, as chemists call it, actually does. Twenty years ago, they thought that once it reached the brain, alcohol elicited its many effects by infiltrating the membranes of neurons there and changing their properties. “Now we know that’s nonsense. You would have to drink 5 liters of schnapps for that to happen,” Spanagel says.

In fact, scientists have learned that alcohol, like other drugs, interacts with the receptors for certain neurotransmitters. But unlike other drugs, it acts on a wide range of them, including receptors for GABA, NMDA, serotonin, and acetylcholine. That will make it hard to find a substance to emulate most of alcohol’s wanted effects while avoiding the unwanted ones, Spanagel predicts.

Nutt is concentrating on the GABA system—the most important inhibitory system in mammalian brains. Alcohol activates GABA receptors, effectively quieting the brain and leading to the state of relaxation many people seek. Nutt has sampled some compounds that target GABA receptors and was pleasantly surprised. “After exploring one possible compound I was quite relaxed and sleepily inebriated for an hour or so, then within minutes of taking the antidote I was up giving a lecture with no impairment whatsoever,” he wrote in a recent article.

But he wants to go one step further. “We know that different subtypes of GABA mimic different effects of alcohol,” he says. Nutt combed the scientific literature and patents for compounds targeting specific GABA receptors, and, in an as-yet unpublished report that he shared with Science, he identifies several molecules that he says fit the bill. Compounds targeting subtypes of the GABAA receptor called alpha2 and alpha3 are particularly promising, he says. Some of these molecules were dropped as therapeutic drug candidates precisely because they had side effects similar to alcohol intoxication.

Gregg Homanics, an alcohol researcher at the University of Pittsburgh, is skeptical that another substance could mimic all the positive effects of alcohol. “You could come up with a drug that might make you feel good. But is it going to be the same good feeling as alcohol? I doubt that.” Such a drug might have downsides of its own, warns Andreas Heinz, an addiction researcher at Charité University Medicine Berlin. It could still turn out to be addictive or to harm a small proportion of the population. “There is an advantage when you have known drugs for hundreds of years and you know exactly what they do,” he says.

Still, Nutt’s appearance on the BBC radio program attracted new investors, ranging “from Ukrainian brewers to American hedge funds,” he says, and Imperial Innovations, a company that provides technology transfer services, is working with him “to consider a range of options for taking the research forward,” a spokesperson says. “We think we have enough funding now to take a substance all the way to the market,” Nutt says—in fact, he hopes to be able to offer the first cocktails for sale in as little as a year from now.

Even a very good alcohol substitute would face obstacles. Many people won’t forsake drinks they have long known and loved—such as beer, wine, and whiskey—for a new chemical, Spanagel says. The idea will also trigger all kinds of political and regulatory debates, Rehm says. “How will such a new drug be seen? Will you be able to buy it in the supermarket? In the pharmacy? Will society accept it?”

Whatever the outcome, Nutt’s quest for a safer drink has already made people think about alcohol in a new way, Rehm adds. “It’s provocative in the best sense of the word.” Much the same could be said of the scientist who thought it up.

http://www.sciencemag.org/content/343/6170/478.full