Psychedelics pioneer keeps his inner hippy in check
After giving people LSD and psilocybin, Robin Carhart-Harris is convinced of psychedelic therapy’s potential – but he daren’t get too excited about it
ONE of the last times I saw Robin Carhart-Harris, I was absolutely off my head on MDMA. On a Monday morning. He knew, because he was the one who gave it to me. He scanned my brain, put me through some psychological tests, and talked to me for what felt like hours about how I was feeling. I remember him being calming and patient. Then again, I was on drugs.
Today I’m completely straight, but he is still calming and patient. It’s a character trait that must come in
It was quite a comedown in the 1970s when research into psychedelic medicine was virtually shut down in the West. Many countries were beginning to classify psychedelics as “schedule 1”, making them illegal, on the grounds that they were drugs of “abuse” with no agreed-upon medical use.
The stigma, and many obstacles, remain. For many people – crucially those who hold the purse strings – research into psychedelic drugs has a whiff of disreputability about it. As our exclusive interview with Robin Carhart-Harris of Imperial College London reveals, anyone daring to lead this science has to perform a balancing act, with their reputations always on the line.
Nevertheless, the field is showing the green shoots of a renaissance. Here’s a round up of New Scientist’s coverage on the potential, the people and the politics of psychedelic medicine….
Many creators of psychedelic drugs famously tested their products on themselves first. Alexander Shulgin, considered the world’s foremost “psychonaut”, is among those featured in our gallery of self-experimenters.
For almost 50 years LSD was banned worldwide and under no circumstances was any scientific experimentation allowed. Only now are we starting to take another look at this long neglected area of science. David Nutt is the man pioneering this rediscovery. His LSD brain imaging experiment has been called the discovery of 2016, more important even than the discovery of gravitational waves. His team at Imperial College London are beginning to unlock the many secrets of our brains and are finding new ways in which psychedelic substances such as psilocybin and LSD could be used to cure mental health disorders. These substances remain a mysterious void in human knowledge, and as a society we are perhaps rightfully wary of them. But the thought of venturing into the unknown has never stopped scientific progress before, and David Nutt is one man intent on shedding light in this expanse of darkness.
So you used to work as a government adviser. What did that life teach you about how the government approaches drugs, as opposed to what you’re doing now? There must be a huge gap.
Yes, there is an enormous gap. That was the great dissolution and that’s why I got sacked. I spent nine years chairing a committee that did the most systematic analysis of drug harms that has ever been done. It developed new methodologies, published papers, and that was enormously fruitful. I believe that’s what governments should do if they want to make good laws. But it gradually became clear to me during that decade that I was working there that they weren’t interested in the facts. They were very happy with the facts that justified their preconceptions, but the facts that conflicted with their preconceptions they tried to dismiss, or hide, or ignore. In the end it became too oppressive. I suddenly discovered one day, during an interview with one of the BBC home affairs correspondents that I was actually speaking like them. I suddenly thought – who is saying these things? This is not me. I had to stop the interview and say, no we can’t go on. Then I started telling the truth and within six months I was sacked.
You are very enthusiastic about green-lighting trials in this area and understandably so. We’re talking about people suffering from anxiety and depression. The Default Mode Network is generally overactive in people with those disorders and Psilocybin has been shown to turn off the DMN and allow the brain to behave in ways never seen before. But we still know very little for certain. Isn’t that terrifying?
The point is we don’t know about it because no one has done it before. It’s quite fascinating. Getting some of this stuff published has been quite difficult. A lot of scientists would prefer if this whole thing went away. It raises challenges to philosophies and theories of science. It is like Einstein. We had a nice theory of physics and then suddenly relativity comes along and we have a different theory. Similarly we had a nice theory of consciousness but then our work comes along and says actually there’s another kind of psychedelic consciousness and that’s associated with very different brain activity. All the scientists working in the area of consciousness are saying, “Hey, get out of here. You’re a fucking psychiatrist.” But the truth is we’ve challenged things and shaken things up.
“I’m sure that within ten years psilocybin will be an accepted alternative treatment for depression.”
The idea of incorporating music into psychedelic therapy isn’t new; it was a point of great interest to music therapists in the 60s. But Kaelen is trying to ground it in a solid scientific framework.
He explained that the need to include music in these trials is borne directly from the rising interest in studying psychedelic drugs and considering how they could be used therapeutically: One of the main purposes of the Imperial College team’s research with these substances is to explore how they might be used to help treat mental illnesses such as depression.
In recent trials, it’s been Kaelen’s responsibility (among other things) to design the perfect playlist for a scientifically-sanctioned psychedelic trip with strict research requirements—a task that requires both a creative sensibility and a respect for the rigorous framework of scientific procedures.
Mendel Kaelen, a PhD student in neuroscience at Imperial College, has led several studies investigating the combined influence of music and psychedelic drugs in human trials. One of the challenges? Choosing the music.
Since its 60s counterculture heyday, LSD has been closely associated with music. But it’s not just artistic proclivities that link them: Researchers have found that listening to music can actually affect the LSD experience on a neurological level—and they have brain scans to back it.
Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging.
Here, three complementary neuroimag-ing techniques: arterial spin labeling (ASL), blood oxygen level- dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects.
Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however.
Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ ego-dissolution ” and “ altered meaning, ” implying the importance of this particular circuit for the maintenance of “ self ” or “ ego ” and its processing of “ meaning. ” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value.
The present results contribute important new insights into the characteristic hallucinatory and consciousness altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
Robin Carhart-Harris, Mendel Kaelen and David Nutt consider a big question on several levels
The ‘classic’ hallucinogens – such as LSD (derived from ergotamine found in ergot fungi), dimethyltryptamine (DMT, the major hallucinogenic component of ayahuasca) and psilocybin (from magic mushrooms) – possess a unique and arguably unrivalled potential as scientific tools to study the mind and the brain.
For those of us who are currently fortunate enough to be researching them, there is a real sense that we are exploring something destined to become the ‘next big thing’ in psychopharmacology. But how much do we really know about how they act on the brain to produce their many unusual effects? Here, we summarise the relevant research, beginning at the level of single neurons and moving towards networks in the brain.
The level of single neurons
All classic hallucinogens stimulate a particular serotonin receptor subtype expressed on neurons in the brain, the serotonin 2A receptor. This receptor appears to be central to the action of hallucinogens because blocking it (with another drug called ketanserin) abolishes the occurrence of the hallucinatory state (Vollenweider et al., 1998). Also, the affinity (or ‘stickiness’) of different hallucinogens for the serotonin 2A receptor correlates positively with their potency, or ‘strength’; for example, LSD has an extremely high affinity for the serotonin 2A receptor and is remarkably potent (Glennon et al., 1984). That hallucinogens ‘stimulate’ serotonin 2A receptors means that they mimic the action of serotonin at the receptor by binding to it, altering its conformation or ‘shape’, and ultimately altering the internal conditions and therefore behaviour of the neuron it sits on.
For the serotonin 2A receptor, the key functional effect of its stimulation is an increase in the excitability of the hosting neuron. Serotonin 2A receptors are primarily expressed on an important type of neuron or brain cell in the brain, excitatory pyramidal neurons. More specifically, serotonin 2A receptors are especially highly expressed on excitatory pyramidal neurons in ‘layer 5’ of the cortex. The cortex is organised into layers of different cell types, like the different layers of a cake, and layer 5 is a deep layer, nearer the base than the icing (Weber & Andrade, 2010). Layer 5 pyramidal neurons are especially important functional units in the brain as they are the principal source of output from a cortical region. They project to hierarchically subordinate, or ‘lower’, cortical and subcortical regions (e.g. from a visual association region to the primary visual cortex).
Layer 5 pyramidal neurons project heavily onto inhibitory interneurons and so the net effect of their excitation seems to be inhibitory (Bastos et al., 2012). This is important because hallucinogen-induced excitation of layer 5 pyramidal cells has been interpreted by some as evidence of a more general excitatory effect of these drugs, but as will be discussed in the forthcoming sections, recent animal electrophysiological and human neuroimaging recordings have cast further doubt on the assumption that hallucinogens have a general excitatory effect on cortical activity (Carhart-Harris et al., 2012; Wood et al., 2012).
Captured by the idiom ‘failing to see the woods for the trees’, these results are a reminder that one should not be too hasty to extrapolate from the activity of certain single units in the brain, since the interconnected nature of cortical circuits means that local excitation can translate into net inhibition, or rather ‘disorder’, at a higher level of the system. If John Donne was a neuroscientist, he might have said: ‘no neuron is an island, entire of itself’.