Baseline (Prevention)

Dissociatives include ketamine, MXE, PCP, 3-MeO-PCP, DXM, and nitrous oxide. All antagonize NMDA receptors; some also affect sigma, dopamine, or opioid systems.

• Limit use to no more than once per week

• Rotate compounds with differing pharmacokinetics (e.g., ketamine vs. DXM)

• Avoid polyuse

Active Tachyphylaxis

When tolerance builds:

• NMDA receptors become hypofunctional

• Dopaminergic rebound may occur

• Cease use for 2–3 weeks minimum

• Use:

  • Magnesium

  • Zinc

  • Memantine to stabilize glutamatergic tone

• Avoid GABAergics during this period to prevent mood destabilization

Withdrawal Transition

• Support recovery with:

  • Taurine

  • Magnesium L-threonate

  • Glycine

  • Creatine

• Consider agmatine (500–1000 mg, PRN) to modulate NMDA without full antagonism

• Use B-vitamins and alpha-GPC to restore acetylcholine tone if cognition is impaired from dissociation

Neurorestoration Phase

• Stimulate BDNF with:

  • Aerobic activity

  • Lion’s mane

  • 7,8-DHF

  • Uridine

• Add:

  • Omega-3s

  • Citicoline

  • Rhodiola

• Maintain dopaminergic tone with phenylalanine or tyrosine as needed

• Reset sleep-wake cycle with melatonin or low-dose agomelatine

Maintenance / Reinforcement

• Keep recreational use spaced out — at least three weeks between sessions

• Maintain magnesium and zinc as baseline neuroprotection

• Avoid combining dissociatives with depressants

• If rotation is needed, use serotonergic or psycholytic agents — but avoid cycles that lead to dopamine overload