Overview of the Depressant Drugs
Mind altering depressant drugs are a broad category of compounds which act on the central nervous system (CNS). Unlike the excitatory role of stimulants, depressants play an inhibitory role on neurotransmission within the CNS, particularly at the brain and spinal cord level. The inhibitory effects of depressants are mediated through different mechanisms; Most traditional depressant drugs, namely barbiturates and benzodiazepines, produce inhibition by one or both of the following means; A) agonism of an inhibitory receptor, or B) antagonism of an excitatory receptor.
GABA receptors mediate inhibition of the central nervous system; and bind the natural neurotransmitter gamma-aminobutyric acid, a GABA agonist. These receptors play a braking role on the nervous system, by slowing or stopping the firing of other neurotransmitters. Activation of GABA receptors at post synaptic sites inhibits the transduction of the neurotransmission which it receives, while activation of presynaptic GABA receptors inhibits neurotransmission into the synaptic cleft and on to the post synaptic neuron. GABA activity at both pre and post synaptic sites leads to a decrease in function of a particular visceral, brain, or spinal area. GABAergic drugs play many roles in therapy and recreation, generally for their anxiolytic, sedative, hypnotic, amnesic, and emotional-blunting effect.
GABA is not the only means of inhibitory transmission. CNS inhibition is acheived with the use of an NMDA receptor antagonist. NMDA receptors rely on the binding of two main neurotransmitters, N-methyl-D-aspartate and glutamate. The NMDA receptor serves the functional role of a gatekeeper of neurotransmission; its activation via NMDA agonists allows the neuro-channels to open, thus allowing the flow of transmission throughout the brain and spinal cord. Therefore, by blocking the NMDA receptor with the use of an NMDA antagonist drug, the "gate" becomes closed; blocking this flow of neurotransmission. This blocking of excitatory function results in an overall inhibition of function in a particular area; visceral, spinal, or brain.
CNS Depressants are widely used in medicine to control; acute anxiety and panic, hypertension and muscle spasms, convulsions or epileptic disorders, as well as pain and isomniatic sleeping disorders. Depressant drugs are often used as general anaesthetics in the surgical setting.
Traditional Depressants (By Pharmacological Class)
Barbiturates - GABA agonist
Benzodiazepines - GABA agonist
Alcohol - GABA agonists, NMDA antagonist, nACh antagonist
Ether - GABA agonist
Dissociative Anaesthetics - NMDA antagonist, Sigma agonist
Volatile Anaesthetics - GABA agonist
In low to moderate doses, classical depressants inhibit cognitive functions of the higher cortical areas, including intelligence, reasoning & judgement, while progressing with higher doses to inhibit sensory perception and motor coordination. With increasing doses generally comes further inhibition of increasingly vital functions.
As doses progress, depressants begin to affect the autonomic nervous system, causing an inhibition of sympathetic "arousal" - including the sympathetic "fight or flight" response to stress; characterized by physiological symptoms of panic or anxiety. Benzodiazapines are used in therapy for this purpose, and are effective in treating acute symptoms of anxiety or panic. Casual use of alcohol produces the same effect. In a much greater capactiy, this additionally proves useful in anaesthesia - An adequate degree of sympathetic inhibition will block the visceral response of the body (response of the organs) to stress, in this case being the pain of surgery. GABA agonist or NDMA antagonist drugs are classically used as general anaesthetics. Benzodiazapines, barbituates, or volatile ethers may be used as general anaesthetics, as well as the NMDA antagonist ketamine. One of the earliest volatile anaesthetics to be used was diethyl ether, a highly potent relative to ethyl alcohol, which has since been replaced by halogenated ethers such as the 'fluranes'. Even alcohol in blood concentrations greater than 0.4 may produce deep anaesthesia adequate for surgery.
Care must be taken; Given in excess, depressant drugs will inhibit autonomic functions completely; meaning respiratory depression, respiratory arrest, heart failure, cardiac arrest, brain death or coma, and death. Excessive doses of benzodiazepines, barbiturates, and even alcohol, will effectively put your brain stem to sleep.
Depressant drugs may act through other mechanisms aside from GABA and NMDA receptors. CNS depression is achieved with the use of anticholinergics, first generation antihistamines, or adrenergic (a2 receptor) antagonists. Ethyl alcohol exhibits additional activity as an NAcH antagonist. Older antihistamines such as diphenhydramine have sedative-hypnotic qualities, while adrenergic antagonists such as beta blockers or clonidine inhibit the sympathetic response to stress and anxiety, causing a physiologically calming effect (often useful in opioid withdrawal or panic attacks).
Depressants drugs for recreational use may fall into several categories, and generally target GABA, GABA receptors, and/or NMDA receptors, Kappa receptors, or Sigma receptors for their pharmacological effects. Alcohol is undoubtedly the most widely used depressant, and most popular recreational drug throughout the world, while other depressants are available in either pharmaceutical form, or clandestinely manufactured illicit form.
Are Opioids Depressants?
Opioids are often classified as CNS depressants, though they are more of a borderline case, and in moderate doses do not produce the typical cognitive/psychomotor impairing effects of a "downer". While typical opioid agonists inhibit certain pathways at the spinal level, they paradoxically produce excitation at the mesolimbic level; inhibiting GABA's braking effect on mesolimbic dopamine firing thus increasing dopaminergic firing and exciting the brain's "pleasure centers". Their subjective effects in a given setting will determine their functional role; low or moderate doses may produce euphoria and excitement without psychomotor or cognitive impairment, observed clinically an improvement in function; while high doses may produce increasing sedation & respiratory depression or in some cases, deep anaesthesia.