Opioid

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Death may occur when opiates are combined with other depressants such as benzodiazepines, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1]

It is strongly discouraged to combine these substances, particularly in common to heavy doses.

Common substances that affect the u-opioid receptor: morphine, codeine, diacetylmorphine (Heroin), naloxone (Narcan), methadone, tramadol.
Poppy pod scored to release opium latex
Dried pods for preparation of tea or solvent extraction of alkaloids

Opioids are psychoactive substances that resemble morphine or other opiates in their pharmacological effects.[citation needed] Opioids work by binding to opioid receptors, which are found in the central and peripheral nervous system and the gastrointestinal tract.[citation needed] The receptors in these organ systems mediate both the beneficial effects and the side effects of opioids.

Although the term opiate is often used as a synonym for opioid, the term opiate is limited to drugs derived from the natural alkaloids found in the resin of the opium poppy (Papaver somniferum).[2] While opioid is a more general term for substances that act primarily on opioid receptors, including natural occurring alkaloids, synthetic substances and opioid peptides.[3]

Opioid dependence can develop with ongoing administration, leading to a withdrawal syndrome with abrupt discontinuation.[4] Opioids are not only well known for their addictive properties, but also for their ability to produce a feeling of euphoria, motivating some to use opioids recreationally.

Chemistry

Opioids are based upon morphine and opium-like structures. They work via their similar chemical structures to the endogenous opioids in the body. Morphine derived opioids, known as morphinans, contain a benzene ring attached to two partially unsaturated cyclohexane rings (phenanthrene) and a 4th nitrogenous ring attached to the core at carbons 9 and 13. There are several classes of opioids which differ greatly in structure from each other. For example, fentanyl and its analogues are structurally unique from morphinans and tramadol derivatives.

Pharmacology

Metabolic pathway of codeine and morphine courtesy of Pharmgkb.org

Opioids are known to mimic endogenous endorphins. Endorphins are responsible for analgesia (reducing pain), causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or excitement. This mimicking of natural endorphins results in the drug's euphoric, analgesic (pain relief) and anxiolytic (anti-anxiety) effects.[5]

Receptor types

Opioids act on the three main classes of opioid receptor in the nervous system, μ, κ, δ (mu, kappa, and delta).[6] Each opioid is measured by its agonistic or antagonistic effects towards the receptors, with the responses to the different receptor sub-types (e.g., μ1 and μ2) providing even more effects. Opioid receptors are found mainly within the brain, but also within the spinal cord and digestive tract.[7]

Delta (δ)

The delta receptor is responsible for the analgesia, antidepressant and convulsant effects as well as physical dependence.[6]

Kappa (κ)

The kappa receptor is responsible for the analgesia, anticonvulsant, dissociative and deliriant effects as well as dysphoria, neuroprotection and sedation.[6]

Mu (μ)

The mu receptor is responsible for analgesia, physical dependence, respiratory depression, euphoria, and possible vasodilation.[6]

Nociceptin

The nociceptin receptor is responsible for anxiety, depression, appetite and development of tolerance to μ agonists.[8][9]

Zeta (ζ)

The zeta opioid receptor, also known as opioid growth factor receptor (OGFr) is responsible for tissue growth, neural development, and is further implicated in the development in some cancers.[10][11][12][13][14][15] The endogenous ligand for OGFr is met-enkephalin, which is also a powerful endogenous delta opioid receptor agonist.[16]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Cognitive effects
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Visual effects
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Pharmacological classes

Naturally occuring
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Semi-synthetic
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Toxicity and harm potential

The short-term non-chronic use of opioids is not associated with any physical or neurological toxicity.[citation needed]

Long term effects

The long-term use of opioids causes hormonal imbalance in both men and women.[17] In men, this opioid-induced androgen deficiency results in abnormally low levels of sex hormones, particularly testosterone.[18]

This negative change in endocrine function in males can lead to: reduced libido, erectile dysfunction, fatigue, depression, reduced facial and body hair, decreased muscle mass, and weight gain.

It is strongly recommended that one use harm reduction practices when using this class of substances.

Tolerance and addiction potential

Due to the highly euphoric nature of these substances, the recreational use and abuse of opioids has an extremely high rate of addiction and dependence. This is combined with a tolerance which builds up quickly, necessitates that the user take increasingly high dosages in order to get the same effects.

The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance.[19] To account for this lack of tolerance, it is safer to only dose a fraction of one's usual dosage if relapsing. It has also been found that the environment one is in can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment.[20]

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

  • Depressants (1,4-Butanediol, 2M2B, alcohol, barbiturates, benzodiazepines, GHB/GBL, methaqualone) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another 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.
  • 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 opioids, which are depressants, with stimulants due to the risk of excessive intoxication. Stimulants mask the sedative effect of heroin, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of heroin will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only taking a certain amount of heroin.

See also

External links

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. Hemmings, Hugh C.; Egan, Talmage D. (2013). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print (in English). Elsevier Health Scienc,es. p. 253. ISBN 1437716792. Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists). 
  3. Hemmings, Hugh C.; Egan, Talmage D. (2013). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print (in English). Elsevier Health Sciences. p. 253. ISBN 1437716792. Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists). 
  4. Cammarano, W. B., Pittet, J. F., Weitz, S., Schlobohm, R. M., & Marks, J. D. (1998). Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Critical care medicine, 26(4), 676-684.
  5. Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (November 2008). "The runner's high: opioidergic mechanisms in the human brain". Cerebral Cortex (in English). 18 (11): 2523–31. doi:10.1093/cercor/bhn013. PMID 18296435. 
  6. 6.0 6.1 6.2 6.3 Opioid - Chapter 2: The Endogeneous Opioid Systems (http://www.stoppain.org / Beth Israel Medical Center's Department of Pain Medicine and Palliative Care) | https://web.archive.org/web/20110719072413/http://www.stoppain.org/pcd/_pdf/OpioidChapter2.pdf
  7. Opioid receptors in the gastrointestinal tract (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163293
  8. Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D (April 2000). "Pharmacology of nociceptin and its receptor: a novel therapeutic target". British Journal of Pharmacology. 129 (7): 1261–83. doi:10.1038/sj.bjp.0703219. PMC 1571975Freely accessible. PMID 10742280. 
  9. Toll L, Bruchas MR, Calo' G, Cox BM, Zaveri NT (April 2016). "Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems". Pharmacological Reviews. 68 (2): 419–57. doi:10.1124/pr.114.009209. PMID 26956246. 
  10. Zagon IS, Wu Y, McLaughlin PJ (August 1999). "Opioid growth factor and organ development in rat and human embryos". Brain Res. 839 (2): 313–22. doi:10.1016/S0006-8993(99)01753-9. PMID 10519055. 
  11. Sassani JW, Zagon IS, McLaughlin PJ (May 2003). "Opioid growth factor modulation of corneal epithelium: uppers and downers". Curr. Eye Res. 26 (5): 249–62. doi:10.1076/ceyr.26.4.249.15427. PMID 12854052. 
  12. Zagon IS, Smith JP, McLaughlin PJ (March 1999). "Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor". Int. J. Oncol. 14 (3): 577–84. doi:10.3892/ijo.14.3.577. PMID 10024694. 
  13. McLaughlin PJ, Levin RJ, Zagon IS (May 1999). "Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor". Int. J. Oncol. 14 (5): 991–8. doi:10.3892/ijo.14.5.991. PMID 10200353. 
  14. Cheng F, Zagon IS, Verderame MF, McLaughlin PJ (November 2007). "The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer". Cancer Research. 67 (21): 10511–8. doi:10.1158/0008-5472.CAN-07-1922. PMID 17974995. 
  15. Donahue RN, McLaughlin PJ, Zagon IS (March 2009). "Cell Proliferation of Human Ovarian Cancer is Regulated by the Opioid Growth Factor - Opioid Growth Factor Receptor Axis". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 296 (6): R1716–25. doi:10.1152/ajpregu.00075.2009. PMID 19297547. 
  16. Christoph Stein (1999). = 4Rfr8cQayvgC&pg = PA22 Opioids in pain control: basic and clinical aspects Check |url= value (help). Cambridge University Press. pp. 22–23. ISBN 978-0-521-62269-1. Retrieved 25 November 2011. 
  17. The effect of opioid therapy on endocrine function. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23414717
  18. Opioid-induced androgen deficiency (OPIAD). (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/22786453
  19. Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
  20. Siegel, S., Hinson, R., Krank, M., & McCully, J. (1982). Heroin “overdose” death: contribution of drug-associated environmental cues. Science, 216(4544), 436–437. https://doi.org/10.1126/science.7200260