Dextromethorphan (DXM): Drug Information

Basic:

DXM is a synthetic morphinan analogue. It is a member of the opioid molecular class but produces no clinically significant opioid effects. DXM was first synthesized in the search of an antitussive with the efficacy of codeine but with lower liability for abuse and dependence. It acts centrally on the cough center in the medulla and nucleus tractus solaris to increase the coughing threshhold, and is one of the most widely used non-prescription medications in the US.

Use:

Originally marketed as a codeine substitute for over the counter antitussiv use, DXM prodiuced no narcotic effect. However, it was soon found to have a higher "abuse" potential than codeine in the recreational sense.

When used in doses exceeding the therapeutic range of 15 to 60mg, it acts as a dissociative anaesthetic drug, producing the effects of ketamine and PCP. These effects become apparent in doses upward of 200mg and occur non linearly, in dose dependent phases or "plateaus" with increasing dose - of which there are four.

Dextromethorphan has proven useful as an adjunct to opioid therapy from chronic pain. Clinical experience has shown that a 1/1 ratio of dextromethorphan to morphine taken on a regular schedule provides superior analgesia to morphine alone, while attenuating development of morphine tolerance. Dextromethorphan may be used for this purpose as an adjunct to any typical opioid. DXM is taken by recreational opioid users with similar results - i.e. a reduced development of opioid tolerance. It may additionally enhance the euphorigenic effects of opioids.

Moderate doses of dextromethorphan (100 to 300mg/day) have been useful in relieving the discomfort of narcotic withdrawal. Its dissociating or numbing effect has been useful in attenuating both physical & psycho symptoms of the abstinence syndrome. DXM is also effective in reducing the psychological 'cravings' in chronic, post-detoxified opiate users experiencing the depressive symptoms of 'post acute withdrawal syndrome' (or simply, the raw misery of sober life) - owing to its monoaminergic & catecholaminergic properties.

Properties:

DXM is molecularly similar in structure to codeine. It is a synthetic compound of the morphinan series. It is the dextrorotatory isomer of the methyl ether of levorphanol, and may be considered a methylated right handed analogue of levorphanol.

DXM is a psychoactive drug of the dissociative anaesthetic therapeutic class. This class includes phencyclidine (PCP or angel dust) and Ketamine (or 'special k'). Drugs of this type are used therapeutically and recreationally to induce a dissociation of the conscious mind from one's body and environment. This is caused by the partial to complete inhibition of sensory input to the conscious mind. This has made such agents useful is surgical or emergency anaesthesia, although their use is less common in humans as it is in animals, due to the bizzarre states of consciousness which have frightened many patients (apparently cats and dogs have not yet reported these effects, much less expressed any complaints)

DXM is a seretonin reuptake inhibitor, a PCP2-receptor agonist, and a sigma receptor agonist. In the higher dose range, DXM is a low efficacy NMDA receptor antagonist - its major metabolite, dextrorphan, is a far more potent NMDA antagonist, and accounts for most of the activity at this site. Activity at NMDA and PCP2 receptors causes dopamine reuptake inhibition in the nucleus accumbens, lending to its euphoric, exciting, stimulant like effects in lower doses (1.5-2.5mg/kg). The effects of the drug are mediated via both dextromethorphan & its major metabolite dextrorphan.

Activity of the NMDA receptor in the simplest of terms, allows for the communication of signals between neurons and the brain; when NMDA receptors are active or "open" (which requires binding of glutamate), they allow neurons to transfer signals freely.

Many dissociative agents share similar pharmacological properties, acting as antagonists to the NMDA receptor; inhibiting the binding of excitatory neurotransmitters such as glutamate - the intricate workings of NMDA mechanisms is quite complex. Their purpose is to mediate the polarization of cellular channels which allow the transfer of signals between neurons. The NMDA receptor essentially works as a gatekeeper at the post-synaptic membrane. Activation of an NMDA receptor keeps channels open, while inhibition of NMDA receptors causes channels to close; by blocking of the post synaptic ion channel inhibits the potential of the nerve cell to fire upon receiving synaptic neurotransmission (from the axon terminals of another neuron).

Effects and Side Effects:

Dopaminergic effects of DXM are most prominent in the lower range of recreational doses. Increased synaptic dopamine in the VTA and nucleus accumbens produces euphorigenic & reinforcing effects. Dextromethorphan in this dose range, also known as the first plateau, produces an invigorating state of pleasure similar to stimulants such as cocaine. Auditory stimulation such as music is extremely pleasant, while motor stimulation such as movement (walking, dancing, etc) is desireable as well. As doses progress, PCP2 mediated dopaminergic effects begins to plateau.

In midrange doses, often known as the second plateau, sigma activity is more pronounced. There is increasing alteration of sensory perception and memory. Brain-motor coordination is affected, leading to a robotic-like movement of arms and legs which is especially apparent when walking. the sensation may be described as attempting to walk in zero gravity, and struggling for one's feet to touch the ground. Psychotomimetic (psychotic-like) effects may be present at this dose. Antagonism at NMDA & sigma receptors impairs the mediating of memory and the brain's ability to coordinate communication between conscious mind and data storage sites in the brain - one has no sense of time, and is often able to perform repetitive or mundane tasks without becoming bored; this may include staring at a wall, or masturbation (joking. jacking off while tripping might be dangerous). Abstract or bizzarre though patterns may become obvious to others, while the user may not perceive it this way. Inhibition of sensory input begins at this level, marked by choppy communication from the body and senses to the brain - Events may be perceived in the mind seconds or minutes after they happen, or may not be experienced at all. One may experience tunnel vision, and perceive ones self as something or someone else, while struggling to understand "what one's environment actually is" - defined best as the complete loss of ones awareness of the nature or existence of one's environment or "existence" in general.

In much higher doses, most effects of the experience are mediated solely by NMDA antagonism and its sensory inhibition. Perhaps the most bizzare effect at this dose level are the increasing gaps in sensory input; this means literally what it sounds like - all physical and environmental perception experiences cut-offs; the best way to describe this experience is simply; an irregular and bizzare state of consciousness where rather than awareness of one's body or environment, there is awareness of nothing; this may be experienced as a complete 'white out' phase, or the complete loss of self awareness. This may be accompanied by strange, disconnected behavior, or no physical movement at all.