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It is strongly discouraged to combine these substances, particularly in common to heavy doses.
The core structure of benzodiazepinesXanax (alprazolam) 2 mg tri-score tablets
Benzodiazepines (also referred to as benzos) are psychoactive drugs that act as central nervous system depressants. These drugs work by magnifying the efficiency and effects of the neurotransmitter gamma-aminobutyric acid (GABA) by acting on its receptors.[2] The prominent effects of benzodiazepines include anxiety suppression, sedation, muscle relaxation, disinhibition, sleepiness and amnesia. Short-acting benzodiazepines are recommended for treating insomnia while long-acting ones are recommended for the treatment of anxiety disorders.
It's worth noting that the sudden discontinuation of benzodiazepines can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.[3] It is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.[4]
Benzodiazepine is a heterocyclic compound comprised of a benzene ring fused to a seven member nitrogenous diazepine ring. Benzodiazepine drugs contain an additional substituted phenyl ring bonded at R5, resulting in 5-phenyl-1,4-benzodiazepines with different side groups attached to the structure to create a number of drugs with different strength, duration and efficacy.
Benzodiazepine drugs commonly contain an aromatic electrophilic substitution such as aromatic halogenation or nitration on R7 of their rings. Benzodiazepines can be subdivided into triazolobenzodiazepines and ketone substituted benzodiazepines. Triazolobenzodiazepines contain a triazole ring bonded to the benzodiazepine structure and are distinguished by the suffix "-zolam." Ketone subsituted rings contain a ketone oxygen bond at R2 of their benzodiazepine structure and are distinguished by their suffix "-azepam."
Pharmacology
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors.[5] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of benzodiazepines on the nervous system.
The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.[6]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠. These effects are listed and defined in detail within their own dedicated articles below:
Sedation - In terms of energy level alterations, these drugs have the potential to be extremely sedating and this often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
Paradoxical effects
Paradoxical reactions to benzodiazepines such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).[8][9]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[10][11]
Emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics.
Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.
The dosages below represent approximate equivalent dosages between various benzodiazepines in comparison to 10mg of diazepam.
The authors of this table specifically state that their equivalents differ from those used by other authors and "are firmly based on clinical experience during switch-over to diazepam at start of withdrawal programs but may vary between individuals."[12]
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[13]
Benzodiazepines have a low toxicity relative to dose.[14] However, they are [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
It is strongly recommended that one use harm reduction practices when using this class of compounds.
Tolerance and addiction potential
Benzodiazepines are extremely physically and psychologically addictive.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use.[15] After cessation, the tolerance returns to baseline in 7-14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing one's usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.[16][17]
Discontinuation
Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of high blood pressure, seizures, and death.[18] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal. Abrupt discontinuation also causes rebound stimulation which presents as anxiety, insomnia and restlessness.
It is safest to reduce the dose each day by a very small amount, for a couple of weeks until close to abstinence. If using a short half-life benzodiazepine, a longer acting variety such as diazepam can be substituted. Symptoms may still be present, but their severity will be reduced significantly. For more information on tapering from benzodiazepines in a controlled manner, please see this guide. Small amounts of alcohol can also help to reduce the symptoms.
The duration and severity of withdrawal symptoms depends on a number of factors including the half-life of the drug used, tolerance and the duration of abuse. Major symptoms will usually start within just a few days after discontinuation and persist for around a week for shorter lasting benzodiazepines. Benzodiazepines with longer half-lives will exhibit withdrawal symptoms with a slow onset and extended duration.
Preparation methods
Volumetric liquid dosing - If one's benzodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the benzodiazepine volumetrically into a solution and dose it accurately based upon the methodological instructions linked within this tutorial here.
↑Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2450203
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