With a few interesting exceptions, the majority of psychoactive compounds tend to have a negative impact on neurogenesis. Of these chronic alcohol use is likely one of the most important and widespread causes of impaired hippocampal neurogenesis. Alcohol intake also increases cortisol levels, having a further knock on effect. Tobacco, stimulants, opiates, entactogens and some psychedelics are associated with a reduction in neurogenesis.
SSRI antidepressants have been found to increase hippocampal neurogenesis, which may play a key role in their antidepressant effect. These antidepressants are only effective for a certain proportion of the population however, they come with a range of side effects and there can be unpleasant and prolonged withdrawal effects following cessation of use. If the increase in neurogenesis is part of the antidepressant effect of these antidepressants, there are certainly healthier and more natural ways of enhancing this process. In the future, new antidepressants may be screened for their neurogenic potential.
Psilocybin has recently been found to increase hippocampal neurogenesis in mice, and increased the speed of their ‘unlearning’ of negative fear behaviour responses when compared to drug free controls. This could mean psilocybin may have applications for treating PTSD in humans, a syndrome characterised by highly abnormal brain function, including impaired hippocampal function.
Studies with high doses of psilocybin have found they can induce long term, positive changes in personality and feelings of life satisfaction and well being. Openness is one of the five measures of personality, and is significantly changed in the long term by psilocybin, especially if people have a mystical experience during a session.
This is of great interest, as after the age of 30 personality is thought to be fixed and openness is generally thought to decline with age. This change in personality remained as strong 14 months after the session, and appears to be long term. Openness covers personality traits such as an appreciation for new experiences, broadness of imagination and finding value in aesthetics, emotion and curiosity, with an increased hunger for knowledge.
These changes are associated with enhanced neurogenesis and neuroplasticity. Thus psilocybin has the potential to act as a multifaceted brain tonic, and could have a number of therapeutic applications, yet remains highly illegal and is deemed to have “no medical use and a high potential for abuse” around the world.
Ibogaine is a key alkaloid responsible for the psychoactivity of the root bark of Tabernanthe iboga used for spiritual and healing purposes in central Africa. It has been found to increase levels of GDNF, and in a long term fashion via an autoregulatory, positive feedback loop. The increase in GDNF expression in turn signals neurons to increase levels of mRNA levels to support further GDNF production, and a single dose of ibogaine can increase GDNF expression for weeks, depending on dosage.
Ibogaine is also highly lipophilic (it loves fat) and remains in body tissue for months, gradually being released, further extending its influence on GDNF expression. It appears this increase in GDNF expression is responsible for part of ibogaine’s well known addiction interrupting effects. GDNF infusion has been used in the treatment of Parkinson’s disease, but is an invasive procedure. It may be possible for future compounds to act as pharmacological vectors to increase GDNF expression in the brain in the treatment of Parkinson’s disease and of cognitive pathologies such as addiction.
Plants such as the ayahuasca vine (Banisteriopsis caapi) and Syrian rue (Peganum harmala), are sources of harmine and both have a long history of human use as medicines. Harmine acts as a reversible monoamine oxidase A inhibitor increasing monoamine levels which has an antidepressant effects in humans. Acute administration has been found to increase BDNF levels and induce antidepressant-like effects in rat hippocampus and may suggest a novel pharmacological target for the treatment of depression.
Use of ayahuasca has been found to lead to a long term increase in platelet 5-hydroxytryptamine (5-HT) transporters and recent neuroimaging research has shown changes in brain structure in long term users, with associated beneficial effects, this being indicative of changes in neuroplasticity. DMT is very closely related to psilocybin which has neurotrophic properties, and it has been hypothesised this endogenous compound may play a role in neurogenesis, neuroprotection, brain development and cellular regeneration.