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The past decade has seen the thawing of a half-century moratorium on psychedelic research, allowing scientists to finally start investigating the effects of these intriguing compounds. Cutting-edge technologies have helped us make up for lost time, revealing how substances like LSD, psilocybin (magic mushrooms), and DMT affect brain activity and mental health. Several hypotheses have emerged from these experiments, some of which have become widely accepted, although a new study into the effects of a drug called salvinorin A has now cast doubt on everything we thought we knew about psychedelics.
Defining A Psychedelic
While any substance that alters our state of consciousness can claim to be a psychedelic, scientists tend to bestow the more exclusive title of "classic psychedelic" upon those drugs that interact with a serotonin (the "happy hormone") receptor called the 5-HT2A receptor. Magic mushrooms, LSD, and DMT all come under this category, although other mind-altering substances like salvinorin A do not. Commonly found in the plant Salvia divinorum, this compound produces an extremely intense trip that lasts for about 15 minutes, yet binds to a kappa opioid receptor rather than serotonin receptors.
According to a new study in the journal Scientific Reports, many of the neurological effects that are typically attributed to classic psychedelics are also observed when people take Salvia, indicating that we may need to revise our most popular theories regarding the impact of psychedelics on the brain.
Psychedelics And The Entropic Brain
Starting in about 2012, a wave of brain imaging studies revealed that classic psychedelics all precipitate a more “entropic” pattern of brain connectivity. This is characterized by an explosion of communication throughout the brain, as regions that wouldn’t normally have much to do with one another suddenly start interacting. Simultaneously, established connectivity patterns between certain brain regions break down, with the end result being a disintegration of brain networks.
Studies on psilocybin and LSD have tended to focus on the ramifications of this pheneomenon within the so-called default mode network (DMN), which controls everyday cognition and thought patterns. As the DMN disintegrates under the influence of classic psychedelics, people tend to experience ego-dissolution, whereby they lose the ability to locate themselves as a bound and distinct entity that is separate from the world around them.
However, the theory that DMN disintegration underpins the ability of classic psychedelics to shut down the ego took a knock when it was revealed that drugs like alcohol and cannabis also interact with the DMN, despite the fact that they don’t generate a sense of universal oneness. More significantly, it has now been revealed that Salvia dissolves the DMN in the same way as classic psychedelics, despite not being one.
It would therefore appear that reduced connectivity in the DMN is not unique to classic psychedelics, indicating that the ability of these substances to knock out a person’s sense of self may depend upon some other mechanism.
Could Other Brain Networks Be Involved?
Studying an entropic brain is no easy feat, given the huge proliferation in connectivity that occurs under the influence of psychedelics. It’s therefore pretty difficult to pin down exactly how these substances produce their effects. Nonetheless, one study did note that LSD causes an increase in connectivity within the brain’s somatosensory network, and that this directly influenced the strength of the trip reported by users.
Another study revealed that the brain’s sensory regions tend to become more integrated under the effects of psilocybin. However, a huge amount of research is still needed before we can say with any certainty how psychedelics produce their effects in the brain. What’s clear, though, is that many different brain regions and networks are likely to be involved, with the DMN being just one of these.
Interestingly, research has shown that different brain regions can influence different aspects of ego-dissolution. For instance, one study indicated that decreased connectivity in the hippocampus causes positive experiences of ego-dissolution under the effects of psilocybin, while increased connectivity in the prefrontal cortex generates negatively experienced ego-dissolution. Even more intriguingly, both of these brain regions are associated with the DMN.
Psychedelics And Brain Plasticity
Numerous studies have highlighted the therapeutic effects of psychedelics, with psilocybin having been found to ease depression in treatment-resistant patients, while ayahuasca – a potent psychedelic brew made from the Amazonian vine Banisteriopsis caapi that contains DMT as its primary psychoactive ingredient – has been associated with an increase in mindfulness. Such improvements in mental health have been linked to an increase in cognitive flexibility, whereby users often have greater power to reshape their habitual thought patterns for a period of time after taking a psychedelic.
It seems logical to attribute this to the entropic nature of the psychedelic brain. Indeed, numerous studies have linked this lasting rise in cognitive flexibility to the weakening of rigid patterns of connectivity and the establishment of more expansive and fluid brain activity. However, scientists now believe that this may be only part of the story, and that psychedelics might also increase the brain’s capacity to rewire itself by generating new neurons and synapses.
The continual reshaping of neural pathways within the brain is a measure of its plasticity, and is seen as essential for learning, memory, and the healing of emotional traumas. The process is largely controlled by proteins like brain-derived neurotrophic factor (BDNF), which is essential for the growth and development of nerve cells.
Interestingly, one recent study found that BDNF levels increased in the blood plasma of volunteers immediately after they were given a microdose of LSD. Separate research, meanwhile, found that neurons in a petri dish tend to form more connections once LSD or DMT are added to the mix. The authors of this study also found that DMT increased neuron spine density in the brains of live mice, and that this tended to correlate with improved psychological outcomes such as the ability to overcome conditioned fear and depression.
Another spectacular study revealed that ayahuasca promotes neurogenesis in the mouse hippocampus. If this holds true for humans, then it would suggest that the substance actually stimulates the formation of new neurons in a brain region that is central to learning and memory, with potentially huge implications for cognitive and mental health.
Taken together, these findings indicate that the effects of psychedelics are far from straightforward, and probably involve a number of unique and complex mechanisms. It will likely take us a while to fully illuminate these processes, but based on what we know it’s hardly surprising that these promising substances are generating such excitement.