Dextromethorphan (DXM) Phenibut Orange Discussion: Dextromethorphan (DXM) & Phenibut

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Dextromethorphan (DXM) & Phenibut​

Dextromethorphan (DXM) is a common ingredient in over-the-counter cough medicines. It primarily works by affecting the brain and nervous system. DXM and its active metabolite, dextrorphan, block NMDA (N-methyl-D-aspartate) receptors in the brain. These receptors are involved in the transmission of signals between nerve cells and play a role in learning, memory, and pain perception. By inhibiting NMDA receptors, DXM can produce dissociative effects, which can alter perception and cognition.

DXM is also an agonist at sigma-1 receptors. These receptors are implicated in several neurological processes, including modulation of neurotransmitter release and neuroprotection. Activation of sigma-1 receptors can contribute to the drug's psychoactive and neuroprotective effects.

DXM inhibits the reuptake of serotonin, a neurotransmitter involved in mood regulation. By increasing serotonin levels in the brain, DXM can have mood-altering effects and may contribute to its use in treating certain mood disorders. However, this also raises the risk of serotonin syndrome when combined with other serotonergic agents.

Last, DXM has a weak affinity for opiate receptors, particularly the sigma-1 receptor and, to a lesser extent, the mu-opioid receptor. While it does not produce significant opioid-like effects, this interaction can contribute to its overall pharmacological profile.


Phenibut (β-Phenyl-γ-aminobutyric acid) is a central nervous system depressant and anxiolytic. It was developed in the Soviet Union and is used in some countries as a prescription medication for anxiety, insomnia, and other conditions.

Phenibut is primarily a GABA B receptor agonist. GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the brain. By stimulating GABA B receptors, Phenibut reduces neuronal excitability, leading to its calming and anxiolytic effects. This action is similar to the mechanism of baclofen, a muscle relaxant and antispastic agent.

Also phenibut has some affinity for GABA A receptors, though this effect is less pronounced than its action on GABA B receptors. Modulation of GABA A receptors contributes to its overall sedative and anxiolytic effects.

It can influence dopamine levels in the brain. It has been shown to increase dopamine in the striatum, which might contribute to its nootropic (cognitive-enhancing) and euphoric effects. This dopaminergic activity can also play a role in its potential for abuse.

At least phenibut can block voltage-gated calcium channels, which helps reduce neuronal excitability. This action may contribute to its overall calming and muscle-relaxant effects.


Combining DXM and phenibut can have significant and potentially dangerous effects due to their interactions with multiple neurotransmitter systems.

• Cognitive Impairment: DXM and phenibut both affect cognitive function. Their combination can lead to heightened confusion, memory impairment, and difficulty concentrating.
• Dissociative and Hallucinogenic Effects: DXM, particularly at high doses, can produce dissociative and hallucinogenic effects. Combining it with phenibut may intensify these effects, potentially leading to severe disorientation, visual and auditory hallucinations, and detachment from reality.
• Increased Anxiety and Mood Swings: While both substances can reduce anxiety at therapeutic doses, their combination, especially at high doses, can paradoxically increase anxiety and cause mood swings. This is due to the complex interactions within the brain’s neurotransmitter systems.
• Enhanced Sedation and CNS Depression: Both DXM and phenibut have sedative properties. When combined, these effects can be significantly amplified, leading to profound sedation and CNS depression. This can result in drowsiness, lethargy, and impaired motor coordination.
• Gastrointestinal Issues: Nausea, vomiting, and other gastrointestinal disturbances are common with both substances. Their combination may exacerbate these issues, leading to increased discomfort and potential dehydration.
• Enhanced Euphoria and Risk of Addiction: Phenibut's dopaminergic activity and DXM’s potential to increase serotonin can combine to enhance feelings of euphoria. This heightened euphoria increases the risk of psychological dependence and abuse.
• Increased Risk of Respiratory Depression: High doses of DXM and phenibut can suppress the respiratory system. When taken together, the risk of severe respiratory depression increases, which can be life-threatening.

The combination of DXM and phenibut poses significant risks due to their additive effects on the central nervous system and neurotransmitter modulation. Enhanced sedation, respiratory depression, cognitive impairment, and potential for severe withdrawal are critical concerns. At the time we have not come across confirmed data on acute and fatal conditions associated with this combination.

Considering the above, we recommend treating this combination with great caution.