Talk:Therapeutic index

The therapeutic index varies widely among substances: most forgiving among the opioid analgesics is remifentanil, which offers a therapeutic index of 33,000:1 while diazepam, a benzodiazepine sedative-hypnotic and skeletal muscle relaxant has a less-forgiving index of 100:1 and morphine, a sedative, antidepressant, and analgesic of herbal origin (genus Papaver) has an index of 70:1^[3] (which, however, is still considered very safe).

Less safe are cocaine, a stimulant and local anesthetic, and alcohol, a widely available sedative consumed worldwide – the therapeutic indices for these substances are 15:1 and 10:1, respectively. Other examples of drugs with a narrow therapeutic range, which may require drug monitoring both to achieve therapeutic levels and to minimize toxicity, include: paracetamol (acetaminophen), theophylline, warfarin and lithium carbonate.

Sometimes the term safety ratio is used instead, particularly when referring to psychoactive drugs used for non-therapeutic purposes, e.g. recreational use.^[4] In such cases, the effective dose is the amount and frequency that produces the desired effect, which can vary, and can be greater or less than the therapeutically effective dose.

The Certain Safety Factor is the ratio of the lethal dose to 1% of population to the effective dose to 99% of the population (LD1/ED99).^[5] This is a better safety index than the LD₅₀ for materials that have both desirable and undesirable effects, because it factors in the ends of the spectrum where doses may be necessary to produce a response in one person but can, at the same dose, be lethal in another.

Synergistic effects

A therapeutic index does not consider drug interactions or synergistic effects. For example, the risk associated with benzodiazepines increases significantly when taken with alcohol, opiates, or stimulants when compared with being taken alone.^{[citation needed]} Therapeutic index also does not take into account the ease or difficulty of reaching a toxic or lethal dose. This is more of a consideration for recreational drug users, as the purity can be highly variable.

The concept of a "therapeutic window" or "safety ratio" is sometimes informally applied in the psychonaut and recreational substance using community to communicate the relative degree of risks associated with the use of various psychoactive substances. These typically relate to the likelihood of experiencing desired effects (such as disinhibition, stamina enhancement, sociability enhancement and euphoria in the case of traditional street drugs and, in the case of hallucinogens, sensory distortions, hallucinatory states, and euphoria) relative to the likelihood of experiencing side-effects which can range from extremely discomforting to life-threatening.

While the exact values for the safety ratios of psychoactive substances are rarely, if ever, referenced (and many are not even available given the prevalence of novel substances and the lack of pharmacological and toxicological data on them), the notion of a particular substance possessing a "high" or "low" safety ratio can serve to inform users about whether they want to experiment with a substance given their own personal comfort levels and degree of acceptable risk they are willing to take.

Factors which complicate this include the unreliability of the purity and dosage of drugs obtained from gray or black markets due to a lack of regulatory oversight. Assessing a substance's safety ratio in advance by conducting independent research is considered to be an integral part of responsible drug use given the large variations in potential responses and the range of precautions one can take to mitigate potential risks.

Examples of this include knowing the general dosage of any particular substance liable to put one at risk of an overdose, particularly those that can be sudden and fatal, such as those associated with opioids like heroin and stimulants like cocaine. In the case of hallucinogens, a substance may have a very low safety ratio, such as LSD, which has no established, reasonable lethal dose^{[citation needed]}) relative to a 25x-NBOMe substance, in which the dose needed to produce the desired psychoactivity is only a few multipliers lower than a dose which can produce seizures, coma or death.^{[citation needed]} For this reason, the NBOMe family of psychedelic substances are considered to be significantly more dangerous to use than LSD despite sharing many psychedelic properties that can be difficult to distinguish, particularly for inexperienced users.

Likewise, the three major subclasses of hallucinogens (i.e. psychedelics, dissociatives, and deliriants) are each associated with their own generalized safety ratios. For example, substances in the deliriant subclass such as diphenhydramine, benzydamine, and datura are associated with higher degrees of physical toxicity at doses which produce the desired hallucinogenic effects and are thus considered to have the lowest safety ratio, which means a greater amount of precaution and preparation (harm reduction practices) must be undertaken if one chooses to experiment with them. Psychedelics and dissociatives tend to have higher safety ratios.^{[citation needed]}

It should be noted that this pharmacological concept is limited in its scope when determining the total degree of risk or safety associated with hallucinogen use, as the low risk of physical overdose does not mitigate the profound changes in perception and cognition which when produced, can lead to dangerous delusional, psychotic, or amnesic states leading to behaviors that result in physical or psychological injury or death. Examples of this include walking into moving traffic or driving while intoxicated.

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• Pharmacology portal
• Effective dose

• Therapeutic index (Wikipedia)