By Mitchell Liester and Rachel Wilkenson

The word brings both fear and hope.

We would like to offer support, structure, and clarity to those on the frontlines of neuropsychiatric care concerning the dangers of misuse of this scheduled substance; at the same time, we must acknowledge the promising clinical trial research describing a new mechanism of action for this amazing medicine. Treatment-resistant cases of mental illness seem to be the rule rather than the exception in psychiatric clinics. Traditional therapies often remain ineffective. As anyone in our field is aware, the battle for survival with mental wellness urges us to develop more effective treatment options. However, the frontiers of life bring ever-present risk.

We offer the following clinical observations for outpatient low-dose sublingual racemic ketamine use, specifically commenting on dose, frequency, and target populations. This conversation is especially important in the context of the proliferation of unregulated ketamine clinics that may threaten safe use.

Rather than receptor blockade or ion channel disruption, which have been the suggested mechanisms of action and theoretical path to efficacy for most traditional psychotropics, ketamine and other psychoplastogens (therapeutics that are capable of promoting structural and functional neural plasticity) are hypothesized to achieve lasting change by increasing the production of a protein called brain-derived neurotrophic factor (BDNF). This protein stimulates the brain to produce greater numbers of neurons and more synapses, which are connections between these neurons. Interestingly, these synapses begin as neuronal projections that look like tree branches and are called dendrites (Latin: resembling a tree).

This branching pattern of growth is described mathematically as the Golden Ratio or Fibonacci Sequence. Layer upon layer, synapses microscopically appear similar to the fungi that support plant root systems through a network called mycelium. A comparison of the growth patterns in the brain and in the plant kingdom demonstrates them to be remarkably similar. Furthermore, ketamine has been found to exist in nature, where it is produced by the fungus Pochonia chlamydosporia.

Over our four and a half years of clinical experience using low-dose sublingual racemic ketamine in patients with treatment-resistant........

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