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Morphine

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Fatal overdose 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.

Summary sheet: Morphine
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.

Interactions
Amphetamines
MAOIs
Nitrous
PCP
Alcohol
Benzodiazepines
Cocaine
DXM
GHB/GBL
Ketamine
MXE
Tramadol
Grapefruit


Morphine is a naturally-occurring opioid substance of the morphinan class found in extracts of the poppy, particularly Papaver somniferum.[2] Members of this group produce effects such as sedation, cough suppression, and euphoria when administered.

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

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.[3][4] Long-acting formulations also exist.[5]

The primary source of morphine is isolation from poppy straw of the opium poppy.[6] In 2013 an estimated 523,000 kilograms of morphine were produced.[7] About 45,000 kilograms were used directly for pain, an increase over the last twenty years of four times.[8] Most use for this purpose was in the developed world.[9] About 70% of morphine is used to make other opioids such as hydromorphone, oxycodone and heroin.[10][11][12]

Contents

History and culture

 

This History and culture section is a stub.

As a result, it may contain incomplete or wrong information. You can help by expanding it.

Morphine was first isolated between 1803 and 1805 by Friedrich Sertürner.[13] This is generally believed to be the first isolation of an active ingredient from a plant.[14] Merck began marketing it commercially in 1827.[15] Morphine was more widely used after the invention of the hypodermic syringe in 1853–1855.[16][17] Sertürner originally named the substance morphium after the Greek god of dreams, Morpheus, for its tendency to cause sleep.[18][19]

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.[20]

Binding affinities (Ki)[21]

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

Subjective effects

 
 This subjective effects section is a stub.

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

You can help by expanding or correcting it.

Disclaimer: The effects listed below are cited from the Subjective Effect Index (SEI), which relies on assorted anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
 

Cognitive effects
 

    • Cognitive euphoria - Morphine produces cognitive euphoria that is substantially stronger compared to other opioids such as codeine or tramadol, but weaker than that of heroin, hydrocodone, and oxycodone. The sensation can be described as powerful and all-encompassing feelings of emotional bliss, contentment, and happiness.
    • Anxiety suppression
    • Compulsive redosing
    • Dream potentiation
    • Irritability - While opioids are well known for their ability to improve mood, they can also have the paradoxical effect of increasing the user's sensitivity to irritable stimuli. This can manifest as aloofness and sudden outbursts of anger and aggression (colloquially known as "opiate rage"). It appears to occur more frequently during the comedown of the experience and/or with heavy use.

Visual effects
 

  • Suppressions

    • Double vision - At high doses, the eyes unfocus and re-focus uncontrollably. This creates a blurred effect and double vision that is present no matter where one focuses their eyes. This can be so intense it becomes impossible to read or drive.

    Hallucinatory States

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:

Toxicity and harm potential

Like most opioids, unadulterated morphine does not cause many long-term complications other than dependence and constipation.[22] 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. Morphine presents cross-tolerance with all other opioids, meaning that after the consumption of morphine all opioids will have a reduced effect.

The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance.[23] 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.[24]

Dangerous 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.[25]

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

  • Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
  • Amphetamines - Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest.
  • Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.
  • Cocaine - Stimulants increase respiration rate, which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
  • DXM - Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
  • GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
  • Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
  • MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
  • MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
  • Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.
  • PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.
  • Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present
  • Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice[26]. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected[26]. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.

Legal status

Internationally, morphine is a Schedule I drug under the Single Convention on Narcotic Drugs.[27] It is on the WHO Model List of Essential Medicines, a list of the most important medications needed in a basic health system.[28]

  • Australia: Morphine is classified as a Schedule 8 drug under the variously titled State and Territory Poisons Acts.[citation needed]
  • Austria: Morphine 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]
  • Canada: Morphine is classified as a Schedule I drug under the Controlled Drugs and Substances Act.[29]
  • France: Morphine is in the strictest schedule of controlled substances, based upon the December 1970 French controlled substances law.[citation needed]
  • Germany: Morphine is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.[30]
  • 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).{{citation needed}
  • Netherlands: Morphine is classified as a List 1 drug under the Opium Law.[citation needed]
  • Russia: Morphine is a Schedule II controlled substance.[31]
  • Switzerland: Morphine is similarly scheduled to Germany's legal classification of the drug.[citation needed]}
  • 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.[32]
  • 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.[33]

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. ↑ Dicpinigaitis, P. V., Morice, A. H., Birring, S. S., McGarvey, L., Smith, J. A., Canning, B. J., & Page, C. P. (2014). Antitussive drugs—past, present, and future. Pharmacological Reviews, 66(2), 468-512.
  3. ↑ Morphine Sulfate | http://www.drugs.com/monograph/morphine-sulfate.html
  4. ↑ 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
  5. ↑ Morphine Sulfate | http://www.drugs.com/monograph/morphine-sulfate.html
  6. ↑ 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
  7. ↑ Narcotic Drugs Stupéfiants Estupefacientes 2014 | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  8. ↑ Narcotic Drugs Stupéfiants Estupefacientes 2014 | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  9. ↑ https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  10. ↑ Narcotic Drugs Stupéfiants Estupefacientes 2014 | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  11. ↑ 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
  12. ↑ 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
  13. ↑ 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
  14. ↑ 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
  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. ↑ 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
  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. ↑ 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
  19. ↑ 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
  20. ↑ Stefano, George B Endogenous morphine Trends in Neurosciences , Volume 23 , Issue 9 , 436 - 442
  21. ↑ 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
  22. ↑ Merck Manual of Home Health Handbook – 2nd edition, 2003, p. 2097
  23. ↑ Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
  24. ↑ 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
  25. ↑ Fatal heroin 'overdose': a review (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8997759
  26. ↑ 26.0 26.1 [1]
  27. ↑ List of narcotic drugs under international control | http://www.incb.org/documents/Narcotic-Drugs/Yellow_List/NAR_2011_YellowList_50edition_EN.pdf
  28. ↑ WHO Model List of Essential Medicines | http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1
  29. ↑ Davis's Canadian Drug Guide for Nurses | https://books.google.ca/books?id=0Y8QBAAAQBAJ&pg=PA1409
  30. ↑ http://www.gesetze-im-internet.de/btmg_1981/anlage_iii_61.html
  31. ↑ Постановление Правительства РФ от 01.10.2012 N 1002 (ред. от 09.08.2019) | https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=331879&dst=100271&date=03.12.2019
  32. ↑ Black's Medical Dictionary | https://books.google.ca/books?id=bUnCAwAAQBAJ&pg=PA162
  33. ↑ 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
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