Psychedelic therapy

Microdosing vs. macrodosing

Microdosing, the use of small amounts of psychedelics such as LSD or psilocybin, is often promoted as a method of improving mood and enhancing cognitive functions. However, recent research suggests that macrodosing may be more effective than microdosing, especially because of the role of monoamine oxidase (MAO) in the breakdown of psychedelic substances.

• The role of MAO: This enzyme breaks down neurotransmitters such as serotonin, dopamine and norepinephrine, as well as psychedelic substances. In microdoses, psilocybin is rapidly broken down, resulting in minimal effects. This explains why some studies find no significant benefits over a placebo (source).
• Macrodosing and neuroplasticity: Higher doses of psychedelics remain active longer and can have more profound effects on the brain. They stimulate 5-HT₂A receptors, increase glutamate levels and promote neuroplasticity, which may help treat depression and anxiety.
• Safety and preparation: Because macrodosing can cause intense experiences, a safe environment, breathing techniques and guidance from an experienced tripsitter or therapist is highly recommended.

Psilocybin therapy

Psilocybin, the active ingredient in certain mushrooms and truffles, is being studied in clinical research because of its potential therapeutic applications.

Therapeutic uses of psilocybin:

• Depression: Psilocybin therapy shows potential in treating therapy-resistant depression.
• Anxiety disorders and PTSD: Research indicates that psilocybin may have positive effects in anxiety disorders and post-traumatic stress disorder (PTSD).
• Addiction: Studies suggest that psilocybin may help with addictions to alcohol and tobacco, among others, by reducing cravings and promoting behavioral change.

Structure of a psilocybin session:

A guided session consists of three phases:

1. Preparation: Intake to assess intentions and medical fitness.
2. The Session: Under the guidance of a therapist or trip sitter, the participant ingests psilocybin (often as truffles). The effects begin after 15-30 minutes and last for several hours (source).
3. Integration: The insights gained are discussed and linked to everyday life.

Future perspective:

Psilocybin therapy is not yet a recognized medical treatment and is not reimbursed by health insurance companies. Regulation and the lack of large-scale studies are barriers. In the Netherlands, however, there are options for supervised sessions, and psilocybin therapy is expected to be recognized possibly by 2027.

Glutamate and the prevention of bad trips

Glutamate, an important neurotransmitter, plays a role in learning and neuroplasticity. Psychedelics affect glutamate activity in several ways:

• Glutamate increase via 5-HT₂A: Activation of this receptor increases glutamate release, which stimulates neuroplasticity.
• Brain studies: Research shows that psilocybin causes specific changes in glutamate levels, which affects the psychedelic experience.
• Animal research: Studies on rodents show a strong increase in glutamate, leading to synaptic growth and changes in brain structures.

Glutamate levels are crucial to the difference between a "bad trip" and a "good trip. High levels in the prefrontal cortex can cause anxiety and overwhelm, while regulated levels contribute to euphoria and profound insights. Therefore, set and setting, breathing techniques and experienced guidance important in psychedelic therapies (source).

The importance of lifestyle improvements

In addition to psychedelic use, lifestyle improvements can support mental and physical health. Lifestyle coaching combined with psychedelic therapy can enhance the positive effects and promote long-term well-being.

• Nutrition and exercise: A healthy diet and exercise improve brain function and mood. Omega-3 fatty acids, B vitamins and magnesium play a crucial role in neuroplasticity.
• Sleep and stress management: Adequate sleep and techniques such as meditation can balance the nervous system.
• Mental coaching: Psychedelic therapy has the most impact when combined with coaching or therapy.

More information on this approach can be found in the combination of psychedelic therapy and lifestyle coaching (source).

Conclusion

Although microdosing can have benefits, studies suggest that macrodosing has a more powerful effect on neuroplasticity and therapy outcomes. This is due to MAO's role in the breakdown of psychedelic substances and its stronger impact on brain connections at higher doses.

When using psychedelics, it is important to consider the balance of benefits and risks. Psychedelics can promote neuroplasticity and emotional breakthroughs, but also carry risks, such as anxious experiences and disorientation. Professional counseling and a healthy lifestyle can help maximize the positive effects and minimize the risks. You can obtain this professional guidance in the Netherlands on non-medical grounds from Trip Therapy.