Morphine

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

It is strongly discouraged to consume moderate to heavy dosages of these substances together.

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Summary sheet: Morphine
Morphine
Molecular structure of Morphine
Morphine.svg
Chemical Nomenclature
Common names Morphine, MSContin, Oramorph, Sevredol
Substitutive name Morphine
Systematic name (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
Class Membership
Psychoactive class Opioid
Chemical class Morphinan
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold < 10 mg
Light 10 - 15 mg
Common 15 - 20 mg
Strong 20 - 30 mg
Heavy 30 mg +
Duration
Total 4 - 6 hours
Onset 10 - 30 minutes
Come up 20 - 40 minutes
Peak 2 - 3 hours
Offset 1 - 2 hours









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.

The primary source of morphine is isolation from poppy straw of the opium poppy.

Morphine is a naturally-occurring opioid analgesic found in the alkaloids of the latex of the poppy plant (Papaver somniferum). As with other opioids, it is used as both a pain relief medication and as a recreational substance for the relaxation, anxyiolysis and intense states of physical and cognitive euphoria it can induce. Potentially serious side effects include a decreased respiratory effort and dangerously low blood pressure, which can be fatal mixed with other depressants.[citation needed] If the dose is reduced after long-term use withdrawal may occur. Common side effects of this include drowsiness, vomiting, and constipation. The frequent and regular administration of morphine is associated with escalating tolerance, physical dependence and addiction.[citation needed]

Morphine can be administered orally, intramuscularly, subcutaneously, intravenously, into the space around the spinal cord, or rectally. It reaches its maximum effect is around 20 min when given intravenously and 60 min when given orally while the duration of effect is between three and seven hours.[2][3] Long-acting formulations also exist.[4]

The primary source of morphine is isolation from poppy straw of the opium poppy.[5] In 2013 an estimated 523,000 kilograms of morphine were produced.[6] About 45,000 kilograms were used directly for pain, an increase over the last twenty years of four times.[7] Most use for this purpose was in the developed world.[8] About 70% of morphine is used to make other opioids such as hydromorphone, oxycodone and heroin.[9][10][11]

History

Morphine was first isolated between 1803 and 1805 by Friedrich Sertürner.[12] This is generally believed to be the first isolation of an active ingredient from a plant.[13] Merck began marketing it commercially in 1827.[14] Morphine was more widely used after the invention of the hypodermic syringe in 1853–1855.[15][16] Sertürner originally named the substance morphium after the Greek god of dreams, Morpheus, for its tendency to cause sleep.[17][18]

Chemistry

Morphine, a benzylisoquinoline alkaloid, is an opiate of the morphinan class. Morphine and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called phenanthrene. A fourth nitrogen containing ring is fused to the phenanthrene at R9 and R13 with the nitrogen member looking at R17 of the combined structure. This structure is called morphinan.

Morphine (along with other morphinans) contains an ether bridge between two of its rings, connecting R4 and R5 through an oxygen group. It contains two hydroxy groups (OH-), bound at R6 and R3, and a methyl group located on the nitrogen atom at R17.

Morphine is a precursor for many morphinan drugs, it is used to synthesize codeine through methylation of its R3 hydroxy group, and heroin through acetylation. Other closely related opioids include hydrocodone, oxycodone, and dihydrocodeine. The chemical structure of morphine is the basis of hundreds of opioid derivatives with a wide range of effects.

Pharmacology

Morphine exerts its effects by binding to and activating the μ-opioid receptor as an agonist. This occurs due to the way in which opioids functionally mimic the body's natural endorphins. Endorphins are responsible for analgesia (pain reduction), sleepiness, and feelings of pleasure and enjoyment. 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.

These appear to stem from the way in which opioids 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 effects.

Morphine is produced by the human body in small amounts and acts as an immunomodulator. Endogenous morphine binds preferentially to the μ3 opioid receptor.[19]

Binding affinities (Ki)[20]

  • Mu opioid agonist - 4.9 nM
  • Kappa opioid agonist - 206 nM
  • Delta opioid agonist - 273 nM

Subjective effects

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This subjective effect breakdown is a stub.

As such, it may contain incomplete or wrong information and is still in progress.

You can help by expanding it.

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 injury or death.

Physical effects
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Cognitive effects
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Visual effects
Eye.svg

Toxicity and harm potential

Like most opioids, unadulterated morphine does not cause many long-term complications other than dependence and constipation.[21] Outside of the extremely powerful addiction and physical dependence, the harmful or toxic aspects of morphine usage are exclusively associated with not taking appropriate precautions in regards to its administration, overdosing and using impure products.

Heavy dosages of morphine can result in respiratory depression, leading onto fatal or dangerous levels of anoxia (oxygen deprivation). This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors proportional to the dosage consumed.

Morphine can also cause nausea and vomiting; a significant number of deaths attributed to opioid overdose are caused by aspiration of vomit by an unconscious victim. This is when an unconscious or semi-conscious user who is lying on their back vomits into their mouth and unknowingly suffocates. It can be prevented by ensuring that one is lying on their side with their head tilted downwards so that the airways cannot be blocked in the event of vomiting while unconscious (also known as the recovery position).

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

As with other opiate-based painkillers, the chronic use of morphine can be considered extremely 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 morphine develops with prolonged use, including therapeutic effects. This results in users having to administer increasingly large doses to achieve the same effects. The rate at which this occurs develops at different rates for different effects with tolerance to the constipation-inducing effects developing particularly slowly.

The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance.[22] 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.[23]

Interactions

Morphine is dangerous to use in combination with other depressants as many fatalities reported as overdoses are caused by interactions with other depressant drugs like alcohol or benzodiazepines, resulting in dangerously high levels of respiratory depression.[24]

Legal issues

  • Australia - Morphine is classified as a Schedule 8 drug under the variously titled State and Territory Poisons Acts.
  • Canada - Morphine is classified as a Schedule I drug under the Controlled Drugs and Substances Act.[25]
  • France - Morphine is in the strictest schedule of controlled substances, based upon the December 1970 French controlled substances law.
  • Germany - Morphine is a verkehrsfähiges und verschreibungsfähiges Betäubungsmittel listed under Anlage III (the equivalent of CSA Schedule II) of the Betäubungsmittelgesetz.[26]
  • Switzerland - Morphine is similarly scheduled to Germany's legal classification of the drug.
  • Japan - Morphine is classified as a narcotic under the Narcotics and Psychotropics Control Act (麻薬及び向精神薬取締法, mayaku oyobi kōseishinyaku torishimarihō).
  • Netherlands - Morphine is classified as a List 1 drug under the Opium Law.
  • United Kingdom - Morphine is listed as a Class A drug under the Misuse of Drugs Act 1971 and a Schedule 2 Controlled Drug under the Misuse of Drugs Regulations 2001.[27]
  • United States - Morphine is classified as a Schedule II controlled substance under the Controlled Substances Act with a main Administrative Controlled Substances Code Number (ACSCN) of ACSCN 9300. Morphine pharmaceuticals in the US are subject to annual manufacturing quotas; morphine production for use in extremely dilute formulations and its production as an intermediate, or chemical precursor, for conversion into other drugs is excluded from the US manufacturing quota.[28]
  • Internationally (UN) - Morphine is a Schedule I drug under the Single Convention on Narcotic Drugs.[29] It is on the WHO Model List of Essential Medicines, a list of the most important medications needed in a basic health system.[30]

See also

External links

Literature

  • Schmidt, H., Vormfelde, S. V., Klinder, K., Gundert-Remy, U., Gleiter, C. H., Skopp, G., Aderjan, R. and Fuhr, U. (2002), Affinities of Dihydrocodeine and its Metabolites to Opioid Receptors. Pharmacology & Toxicology, 91: 57–63. https://doi.org/10.1034/j.1600-0773.2002.910203.x
  • Koch T, Höllt V (2008). Role of receptor internalization in opioid tolerance and dependence. Pharmacol. Ther. 117 (2): 199–206. https://doi.org/10.1016/j.pharmthera.2007.10.003
  • Pert, C. B., Pasternak, G., & Snyder, S. H. (1973). Opiate Agonists and Antagonists Discriminated by Receptor Binding in Brain. Science, 182(4119), 1359-1361. https://doi.org/10.1126/science.182.4119.1359
  • Friswell J, Phillips C, Holding J, Morgan CJ, Brandner B, Curran HV (2008). Acute effects of opioids on memory functions of healthy men and women. Psychopharmacology (Berl.). 198 (2): 243–50. https://doi.org/10.1007/s00213-008-1123-x.
  • Stefano GB, Ptáček R, Kuželová H, Kream RM (2012). Endogenous morphine: up-to-date review (2011). Folia Biol. (Praha). 58 (2): 49–56. PMID 22578954. Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla.

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. Morphine Sulfate | http://www.drugs.com/monograph/morphine-sulfate.html
  3. Rockwood, Charles A. (2009). Rockwood and Wilkins' fractures in children. (7th ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. p. 54. ISBN 9781582557847 | https://books.google.ca/books?id=QVIdXV_F8M4C&pg=PA54#v=onepage&q&f=false
  4. Morphine Sulfate | http://www.drugs.com/monograph/morphine-sulfate.html
  5. Narcotic Drugs Estimated World Requirements for 2008, Statistics for 2006. New York: United Nations Pubns. 2008. p. 77. ISBN 9789210481199. | https://books.google.ca/books?id=0_9QHvacPzYC&pg=PA77#v=onepage&q&f=false
  6. Narcotic Drugs Stupéfiants Estupefacientes 2014 | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  7. Narcotic Drugs Stupéfiants Estupefacientes 2014 | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  8. https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  9. Narcotic Drugs Stupéfiants Estupefacientes 2014 | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  10. Triggle, David J. (2006). Morphine. New York: Chelsea House Publishers. pp. 20–21. ISBN 9781438102115. | https://books.google.ca/books?id=sud4ORAMNkYC&pg=PA20#v=onepage&q&f=false
  11. Karch, Steven B. (2006). Drug abuse handbook (2nd ed.). Boca Raton: CRC/Taylor & Francis. pp. 7–8. ISBN 9781420003468. | https://books.google.ca/books?id=F0mUte90ATUC&pg=PA7#v=onepage&q&f=false
  12. Courtwright, David T. (2009). Forces of habit drugs and the making of the modern world (1 ed.). Cambridge, Mass.: Harvard University Press. pp. 36–37. ISBN 9780674029903. | https://books.google.ca/books?id=GHqV3elHYvMC&pg=PA36#v=onepage&q&f=false
  13. Luch A, ed. (2009). Molecular, clinical and environmental toxicology. Springer. p. 20. ISBN 3-7643-8335-6. | http://books.google.com/?id=MtOiLVWBn8cC&pg=PA20
  14. Courtwright, David T. (2009). Forces of habit drugs and the making of the modern world (1 ed.). Cambridge, Mass.: Harvard University Press. pp. 36–37. ISBN 9780674029903. | https://books.google.ca/books?id=GHqV3elHYvMC&pg=PA36#v=onepage&q&f=false
  15. Courtwright, David T. (2009). Forces of habit drugs and the making of the modern world (1 ed.). Cambridge, Mass.: Harvard University Press. pp. 36–37. ISBN 9780674029903. | https://books.google.ca/books?id=GHqV3elHYvMC&pg=PA36#v=onepage&q&f=false
  16. Clayton J. Mosher (2013). Drugs and Drug Policy: The Control of Consciousness Alteration. SAGE Publications. p. 123. ISBN 9781483321882. | https://books.google.ca/books?id=2UQXBAAAQBAJ&pg=PA123#v=onepage&q&f=false
  17. Clayton J. Mosher (2013). Drugs and Drug Policy: The Control of Consciousness Alteration. SAGE Publications. p. 123. ISBN 9781483321882. | https://books.google.ca/books?id=2UQXBAAAQBAJ&pg=PA123#v=onepage&q&f=false
  18. Fisher, Gary L. (2009). Encyclopedia of substance abuse prevention, treatment, & recovery. Los Angeles: SAGE. p. 564. ISBN 9781452266015. | https://books.google.ca/books?id=DFR2AwAAQBAJ&pg=PT598
  19. Stefano, George B Endogenous morphine Trends in Neurosciences , Volume 23 , Issue 9 , 436 - 442
  20. Schmidt, H., Vormfelde, S. V., Klinder, K., Gundert-Remy, U., Gleiter, C. H., Skopp, G., Aderjan, R. and Fuhr, U. (2002), Affinities of Dihydrocodeine and its Metabolites to Opioid Receptors. Pharmacology & Toxicology, 91: 57–63. https://doi.org/10.1034/j.1600-0773.2002.910203.x
  21. Merck Manual of Home Health Handbook – 2nd edition, 2003, p. 2097
  22. Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
  23. 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
  24. Fatal heroin 'overdose': a review (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8997759
  25. Davis's Canadian Drug Guide for Nurses | https://books.google.ca/books?id=0Y8QBAAAQBAJ&pg=PA1409
  26. http://www.gesetze-im-internet.de/btmg_1981/anlage_iii_61.html
  27. Black's Medical Dictionary | https://books.google.ca/books?id=bUnCAwAAQBAJ&pg=PA162
  28. Triggle, David J. (2006). Morphine. New York: Chelsea House Publishers. pp. 20–21. ISBN 9781438102115. | https://books.google.ca/books?id=sud4ORAMNkYC&pg=PA20#v=onepage&q&f=false
  29. List of narcotic drugs under international control | http://www.incb.org/documents/Narcotic-Drugs/Yellow_List/NAR_2011_YellowList_50edition_EN.pdf
  30. WHO Model List of Essential Medicines | http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1