LSD, Neurogenesis, Depression, and Alzheimer's Disease

Humanity is in a dark age of medical knowledge, particularly in dealing with the worst disorders, clinical depression, its traveling partner, anxiety, and the end-of-life horror of Alzheimer's Disease (AD) and other dementias. Older adults with dementia are confined to skilled nursing warehouses, wandering hopelessly in their memoryless journey to death.  Psychiatrists, physicians, and therapists often seem little more than witch doctors in white coats with mountains of pills to dispense, tablets that supply little more help than placebos. 

There is hope, however, in recently published research using hallucinogenic compounds.  Clinical researchers are providing discoveries demonstrating psychedelic compounds can improve neuronal connectivity, stimulate neurogenesis, reinstate brain plasticity, decrease inflammation, and improve cognition.  Research is in its adolescence, though, and it is not time to dial into the dark web and self-prescribe.

Dr. Albert Hoffman, a Swiss Chemist, Synthesized LSD in 1938

Lysergic Acid Diethylamide (LSD) is a compound first synthesized in 1938.  It is an ergot alkaloid extracted from the rye fungus Claviceps Purpurea.
The politically inspired War on Drugs, started by President Richard Nixon in the early 1970s, effectively stopped all clinical LSD research.  LSD is not just a recreational drug; the compound may be another tool to help resolve depression and treat other conditions.  Scientists in the United States have only recently restarted clinical LSD research.  This exploration is in its early stages but points to LSD as a potential agent to encourage neurogenesis, the growth of nerve cells, in the human brain.

Stress and depression, as well as other psychiatric illnesses, cause structural changes in the human brain.  These alterations result from atrophy and loss of neurons and glia in specific limbic regions.  Dendritic loss in neurons is a common feature of stress-related psychiatric disorders, including post-traumatic stress disorder (PTSD), depression, anxiety, and drug addiction. 

Depression is associated with structural alterations in brain zones that manage mood and emotion.  Animal studies of chronic stress and postmortem examinations of brain tissue from depressed human subjects show atrophy and loss of neurons and glial cells.  These findings suggest that depression and stress-related mood disorders may be neurodegenerative ailments. Eliminating stress and the administration of conventional antidepressants can block and even reverse the progression of these structural alterations.  

The logic of using LSD to reverse brain atrophy and improve neurologic conditions is captivating.  For example, if depression causes the atrophy of specific brain parts, then changing that process could be the answer or at least a part of a solution. That logic, however, requires a lot of assumptions, and those assumptions might well be only partially valid.  Moreover, the compound is poorly understood clinically, and research is, at best, in its preliminary stages. 
 
Psychoplastogens, small molecules capable of rapidly encouraging cortical neuron growth, have been posited to cause beneficial effects on behavior by mending these changes.  LSD, a psychoplastogen, may promote sustained growth of cortical neurons, even after limited treatment.
Modern-day studies in the United Kingdom and Switzerland include neuroimaging studies using functional magnetic resonance imaging (fMRI).  LSD administration is associated with extensive alterations in functional brain connectivity, measuring the activities between different brain parts. These results agree with theories that mind-altering treatments exercise their effects by impeding the cerebral sorting of external and internal data.

Microdosing is a New Fad but Evidence is Lacking

Taking low doses of LSD, called microdosing, has hit mainstream conversation.  A microdose is a sub-threshold dose, meaning it's on the threshold of feeling.  Microdosers aim to brighten their mood and increase cognitive abilities, not to feel 'high.' Unfortunately, there is no consensus on what constitutes a microdose, and the subjective and perceptual effects of weighted doses are anecdotal and so problematic.

Positive or negative empirical results about microdosing are debatable, as studies involve only a limited number of doses and have fundamental flaws in their design and the resultant data.

The continued criminalization of psychedelics for public health reasons appears without support.  Despite anti-drug propagandists' attempts to foul the image of hallucinogens, they seem strangely safe.  A recent population study of 130,000 adults in the United States failed to find evidence for a link between hallucinogenic use and mental health problems.
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Lifetime psychedelic use was associated with significantly reduced odds of past-month psychological suffering, past-year suicidal thinking, past-year suicidal preparation, and past-year suicide effort. In contrast, lifetime illicit use of other drugs was primarily associated with an increased likelihood of these outcomes.  These findings provide evidence that psychedelics are not causal elements in suicide and mental health issues, contrary to commonly held beliefs.

Scientists are Scrambling for a Solution to Dementias

The mechanism of AD includes the presence of amyloid-β and tau deposition in the brain, hippocampal atrophy, and heightened rates of hippocampal degeneration over time.  In AD, there is a reduction in global brain glucose metabolism in frontal and temporal-parietal areas.  In addition, all known genetic and environmental risk factors for AD are associated with increased inflammation, suggesting that reducing inflammation could be a target for preventing AD.

Early on, researchers understood psychedelics could be helpful agents for dealing with dementia. As a result, pharmaceutical companies developed ergot alkaloids to help mental recognition and other symptoms related to AD.  Medical practitioners prescribe the FDA-approved ergot-derived drug ergoloid mesylates (Hydergine®), which confers minor improvements in AD treatment.  In addition, physicians use Nicergoline (Sermion®), another ergoline alkaloid, to treat dementia.  Ergot alkaloids are assumed to enhance the blood flow to the brain and modulate the neurotransmitter function.
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Recent research findings are fascinating and provide compelling evidence for more detailed research.  This research may result in clinical breakthroughs to help treat and possibly resolve debilitating psychiatric conditions.  LSD and similar hallucinogens appear to provide little risk when used recreationally, and decriminalization likely provides little public health risk.  Regardless, empirical research is in its infancy, and the self-administration of these compounds to treat complicated clinical conditions is ill-advised.