Dextromethorphan (DXM) & Marijuana
Dextromethorphan (DXM) is a dissociative drug primarily used as a cough suppressant but also known for its psychoactive and hallucinogenic effects at higher doses. It exerts its effects through multiple pharmacological mechanisms, primarily acting as an N-methyl-D-aspartate (NMDA) receptor antagonist, a serotonin reuptake inhibitor, and a sigma-1 receptor agonist.
DXM is metabolized into dextrorphan (DXO) by the cytochrome P450 enzyme CYP2D6. DXO is a more potent NMDA receptor antagonist than DXM itself and contributes significantly to the drug’s dissociative and hallucinogenic properties. NMDA receptors are critical for synaptic plasticity and cognitive function, and their inhibition by DXM and DXO leads to disruptions in glutamatergic neurotransmission. This results in altered perception, cognitive impairment, and dissociative states, similar to the effects produced by other NMDA antagonists such as ketamine and phencyclidine (PCP).
Beyond its NMDA antagonism, DXM also inhibits the reuptake of serotonin, acting similarly to selective serotonin reuptake inhibitors (SSRIs). This serotonergic activity contributes to mood elevation and may enhance the drug’s hallucinogenic effects.
DXM additionally interacts with sigma-1 receptors, which are involved in neuroprotection, mood regulation, and psychotropic effects. Sigma-1 receptor activation may contribute to the drug’s stimulant-like properties, including increased energy, euphoria, and cognitive distortions.
At high doses, DXM and DXO affect the dopaminergic system by modulating neurotransmitter release. While not as directly reinforcing as traditional stimulants, DXM’s effects on dopamine may contribute to its mild addictive potential and influence its psychoactive properties.
The pharmacological effects of DXM depend on the dose, leading to different "plateaus" of experience. Lower doses primarily produce mild euphoria and sedation, while moderate doses induce dissociation, motor impairment, and perceptual distortions. High doses result in profound dissociation, hallucinations, and out-of-body experiences, with effects resembling those of ketamine or PCP.
Marijuana, or cannabis, exerts its effects primarily through interactions with the endocannabinoid system (ECS), a complex network of receptors, endogenous cannabinoids, and enzymes involved in regulating mood, memory, pain, appetite, and other physiological functions. The primary psychoactive compound in marijuana is delta-9-tetrahydrocannabinol (THC), while cannabidiol (CBD) and other cannabinoids contribute to its overall effects.
THC acts as a partial agonist at cannabinoid type 1 (CB1) receptors, which are densely expressed in the brain, particularly in the cerebral cortex, hippocampus, basal ganglia, and cerebellum. CB1 receptor activation inhibits the release of neurotransmitters such as glutamate, GABA, and dopamine by reducing presynaptic calcium influx. This inhibition alters synaptic plasticity, leading to marijuana’s characteristic psychoactive effects, including euphoria, altered perception of time, and impaired memory formation. The activation of CB1 receptors in the mesolimbic dopamine system also enhances dopamine release, contributing to the drug’s rewarding and reinforcing effects.
In contrast, cannabidiol (CBD) has a more complex pharmacological profile. Unlike THC, CBD does not bind strongly to CB1 receptors and instead modulates the ECS indirectly. CBD inhibits the enzyme fatty acid amide hydrolase (FAAH), which breaks down anandamide, an endogenous cannabinoid. By increasing anandamide levels, CBD contributes to anxiolytic and anti-inflammatory effects. CBD also interacts with serotonin 5-HT1A receptors, which may explain its antidepressant and anti-anxiety properties, and with transient receptor potential vanilloid 1 (TRPV1) channels, which play a role in pain perception.
Other cannabinoids, such as cannabinol (CBN) and cannabigerol (CBG), exhibit unique effects. CBN is a mildly psychoactive compound that forms as THC degrades over time, producing sedative effects. CBG, a precursor to both THC and CBD, interacts with CB1 and CB2 receptors and has been studied for its potential neuroprotective and anti-inflammatory properties.
Terpenes, the aromatic compounds in cannabis, also contribute to its effects by interacting with cannabinoid and non-cannabinoid receptors. Myrcene, a common terpene, enhances sedation by facilitating GABAergic neurotransmission, while limonene and pinene may counteract THC-induced cognitive impairment by promoting acetylcholine release.
The combination of DXM and marijuana produces complex interactions due to their overlapping and distinct effects on neurotransmission. Both substances influence glutamatergic, serotonergic, and dopaminergic systems, while also modulating perception, cognition, and mood.
One potential effect of combining DXM and marijuana is a significant intensification of dissociation and altered perception. This could result in extreme derealization and depersonalization, where the user may feel disconnected from their body, surroundings, or sense of self.
The combination may also enhance the hallucinogenic properties of DXM. Marijuana’s ability to modulate serotonin and glutamate signaling may potentiate these effects, leading to a more immersive and potentially overwhelming trip. Some users report that marijuana enhances the introspective and dreamlike aspects of DXM, making the experience feel more psychedelic rather than purely dissociative.
Cognitively, the mixture is likely to cause severe short-term memory impairment and confusion. Users may feel trapped in looping thought patterns or experience thought fragmentation, where ideas rapidly shift and become difficult to grasp.
On an emotional level, the combination can be unpredictable. Some users may experience profound euphoria, relaxation, and enhanced appreciation for music and sensory input. Others may encounter anxiety, paranoia, or even full-blown panic attacks, especially at high doses.
Physiologically, the mixture may increase the risk of dizziness, nausea, and motor impairment. DXM disrupts coordination and balance due to its effects on the cerebellum, and marijuana can enhance these effects by further modulating motor control. Additionally, both substances can elevate heart rate and blood pressure, which may be problematic for individuals with cardiovascular issues.
There is a documented case of acute psychotic disorder resulting from the combined use of marijuana, DXM, and caffeine. A 20-year-old male developed delusions and hallucinations after two days of using these substances together. This suggests that combining DXM and marijuana may increase the risk of severe psychological effects, including psychosis.
Overall, the combination of DXM and marijuana is highly variable and dependent on dosage, individual neurochemistry, and tolerance. The unpredictability of the interaction suggests that caution should be exercised, especially at high doses or in individuals prone to anxiety, dissociation, or cardiovascular issues.
Considering the above, we recommend treating this combination with great caution.
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