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Lorazepam
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Revision as of 12:10, 5 October 2018 by >NaYeahMate(→Subjective effects: Rearranged cognitive effects.)
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
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.[6] 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.[7]
Lorazepam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R1 and R4. Further, the benzodiazepine ring is bonded at R5 to a 2-chlorinated phenyl ring. R7 of the benzyl ring is also substituted with a chlorine group. Additionally, Lorazepam contains a hydroxy (OH-) group substituted at R3. It also contains an oxygen group double bonded to R2 of its diazepine ring to form a ketone. This oxygen substitution at R2 is shared with other benzodiazepine drugs with the 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.[8] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of lorazepam 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.[9]
Lorazepam is thought to have a relatively high affinity for GABA receptors compared to other benzodiazepines, which may also explain its marked amnesic effects.[10]
Lorazepam undergoes glucuronidation via Hepatic Pathways which produces lorazepam glucuronide as the main metabolite. The glucuronide attached increases the polarity of the molecule allowing a faster excretion through urine.[citation needed]
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 ☠.
Appetite enhancement - This effect is not particularly prominent, but is reported to occur in some people. It can have a synergistic effect when combined with cannabis
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%).[13][14]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[15][16]
Cognitive effects
The cognitive effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of lorazepam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressants cognitive effects.
The most prominent of these cognitive effects generally include:
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.
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.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[17]
Lorazepam likely has a low toxicity relative to dose.[18] However, it is [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
Lorazepam is extremely physically and psychologically addictive.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days. However, in certain cases this may take significantly longer in a manner which is proportional to the duration and intensity of one's long-term usage.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see this guide.
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 hypertension, seizures, and death.[19] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Lorazepam presents cross-tolerance with [[Cross-tolerance::all benzodiazepines]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Overdose
Benzodiazepine overdose may occur when a benzodiazepine is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as barbiturates and alcohol since they work in a similar fashion, but bind to distinct allosteric sites on the GABAA receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer[20]. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
Symptoms of a benzodiazepine overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with flumazenil, a GABAA antagonist[21], however care is primarily supportive in nature.
Dangerous interactions
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Stimulants - It is dangerous to combine benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
Legal status
Internationally, lorazepam is a Schedule IV drug under the United Nations Convention on Psychotropic Substances.[22]
Austria: Lorazepam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).[citation needed]
United States: Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S.
Canada: It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada.
United Kingdom: It is a Class C, Schedule 4 controlled drug under the Misuse of Drugs Regulations 2001.[23]
Germany: Preparations containing more than 2.5 mg are controlled under Anlage 3 of the BtMG and require a prescription.
↑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
