Talk:Loperamide

Loperamide is a phenylpiperidine derivative, opioid agonist thought to have a low potential for central nervous effects. It was launched by Janssen Pharmaceutica in 1973. On release loperamide was classified in the US as a schedule II narcotic, before transfer to to schedule V in 1977. In November 1982 loperamide was removed from schedule V or 'decontrolled' and made available over-the-counter.

This appears to have been based on initial, preclinical studies indicative of dependence and withdrawal in animal studies. The consensus of later studies was that loperamide has a low potential for abuse, based on an apparent lack of central nervous effects.

Web and internet forum based discussion of loperamide seems to be focused on two topics related to opioid use; its application in the management of withdrawal and its potential for central nervous effects. Appearing in threads or posts on various forums as early as 2005, there appears to have been a sustained increase in interest in loperamide. According to the report, between 2010 and 2011, there was a 10-fold increase in web forum postings about oral loperamide abuse. Most (70 percent) of the postings discussed using the drug to self-treat a discomforting opioid withdrawal, while 25 percent focused on using loperamide to simply get high. All of this may be having tragic consequences. According to the researchers, there was a 71 percent jump in loperamide abuse/misuse-related calls to poison control centers across the United States between 2011 and 2014.^[8][9][10]

Loperamide is a phenylpiperidine derivative with a chemical structure similar to opioid receptor agonists such as diphenoxylate and bezitramide. Like diphenoxylate, it has a methadone-like structure and a piperidine moiety.^[11]

Loperamide is an opioid-receptor agonist and acts on the μ-opioid receptors in the myenteric plexus of the large intestine. Loperamide works like morphine, decreasing the activity of the myenteric plexus, which decreases the tone of the longitudinal and circular smooth muscles of the intestinal wall. It is considered to have a low abuse potential because of substantial first-pass metabolism and P-glycoprotein-mediated efflux at the level of the blood-brain barrier. Central nervous system opioid effects are not observed after therapeutic oral dosing because of poor bioavailability and minimal central nervous system penetration. However, central nervous system opioid effects do occur after supratherapeutic oral doses.^[12]

Concurrent administration of P-glycoprotein inhibitors such as quinidine potentially allows loperamide to cross the blood–brain barrier and produce central morphine-like effects. Loperamide taken with quinidine was found to produce respiratory depression, indicative of central opioid action.^[13]

Loperamide is metabolized by the cytochrome P450 (CYP) system and is a substrate for the CYP3A4 isoenzyme. Concurrent administration with CYP3A4 inhibitors may elevate loperamide concentrations.^[14]

In comparison to the effects of other opioids, this compound can be described as less euphoric. 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 PsychonautWiki contributors. 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 ☠.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

• Erowid Experience Vaults: Loperamide

Toxicity

Although it is relatively safe at therapeutic doses, increasing reports describe its misuse and abuse at very high doses either for euphoric effects or to attenuate symptoms of opioid withdrawal. The most common presentation of loperamide intoxication is syncope which is caused by serious cardiac dysrhythmia and can lead to death.^[15] Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing.^[16] Features of conventional opioid toxicity may also be present.^[6][12]

The majority of patients had loperamide toxicity due to misuse/abuse, in-line with national trends. In patients avoiding withdrawal, doses >100 mg were observed. When taken in large doses (>200 mg), loperamide may cause significant cardiovascular effects, including QTc-prolongation and ventricular dysrhythmias.^[17]

Since 2015, several reports of sometimes-fatal cardiotoxicity due to high-dose loperamide abuse have been published.^[12][18]

It is strongly recommended that one use harm reduction practices, and take extreme caution when using this substance.

Tolerance and addiction potential

Loperamide is not considered physically and psychologically addictive. However, the development of physical dependence on the drug is potentially possible, since loperamide has been shown to cause a mild physical dependence during preclinical studies, specifically in mice, rats, and rhesus monkeys. Symptoms of mild opiate withdrawal were observed following abrupt discontinuation of long-term treatment of animals with loperamide.^[19] Therefore the chronic use of loperamide can be considered as mildly addictive and is capable of causing both physical and psychological dependence. When physical dependence has developed, withdrawal symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of loperamide develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Loperamide presents cross-tolerance with all other opioids, meaning that after the consumption of loperamide all opioids will have a reduced effect.

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

• Depressants (1,4-Butanediol, 2M2B, alcohol, barbiturates, gabapentinoids, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation and sedation caused by each other and can lead to unexpected loss of consciousness at high doses. There is also 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 - Because loperamide increases BPM and BP and stimulants also do this, cardiac arrest, hypertensive crisis, stroke, and heart attack all become much more likely to occur. Besides it can be dangerous to combine depressants with stimulants due to the risk of accidental excessive intoxication. Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states.
• 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.
• CYP450 3A4 or 2C8 inhibitors - Coadministration with drugs that enhance the gastrointestinal absorption or inhibit the metabolism of loperamide (e.g., potent CYP450 3A4 or 2C8 inhibitors) may increase the plasma concentrations and adverse effects of loperamide. ^[20] That includes; erythromycin, ritonavir, grapefruit.

Loperamide is legal and available in over-the-counter preparations in most parts of the world.

Loperamide can be extracted from the parenting product, usually pills, specifically non gel pills. Loperamide is extracted with ethyl alcohol, when extracted, the resulting product tends to be a green or teal group of crystals, which is loperamide and coloring from the medications manufacture. These crystals are often then removed from the container that they were formed in, and put into a smoking device of some sort, usually a pipe designed for crystalline substances. However according to experience reports from Erowid, extracted loperamide smells very strongly of chemicals, and was compared to the smell that of methamphetamine and crack cocaine.

• Responsible use
• Naloxone
• Opioid
• Methadone

• Loperamide (Wikipedia)
• Loperamide (Erowid Vault)
• Loperamide (Isomer Design)