Dihydrocodeine

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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.

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Summary sheet: Dihydrocodeine
Dihydrocodeine
Dihydrocodeine.svg
Chemical Nomenclature
Common names Dihydrocodeine
Systematic name 4,5-alpha-epoxy-3-methoxy-17-methylmorphinan-6-ol
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 Common Heavy
20 - 50 - 100 - 150 - 200 mg
Light Strong
Threshold 20 - 50 mg
Light 50 - 100 mg
Common 100 - 150 mg
Strong 150 - 200 mg
Heavy 200 mg +
Duration
Total 3 - 4 hours
Onset 30 - 45 minutes









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.

Dihydrocodeine is a semi-synthetic morphinan opioid analgesic prescribed for pain, or as an antitussive (either alone or compounded with paracetamol or aspirin). It was developed in Germany in 1908 and first marketed in 1911.[2]

Dihydrocodeine is also known as Drocode, Paracodeine and Parzone. Its many brand names include Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Dehace, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Makatussin, Nadeine, Novicodin, Rapacodin, Fortuss, Paramol, Remedeine, Dico and DF-118.

Dihydrocodeine is available as tablets, solutions, elixirs, and other oral forms. In some countries, the drug is available as an injectable solution for deep subcutaneous and intra-muscular administration. As with codeine, intravenous administration should be avoided as it could result in anaphylaxis and dangerous pulmonary edema. Dihydrocodeine is available in suppository form on prescription.

Dihydrocodeine is used as an alternative or adjunct to codeine and is similar in chemical structure. Depending on individual metabolism, dihydrocodeine is 100 to 150 percent as strong as codeine.

Chemistry

Dihydrocodeine, or 4,5-alpha-epoxy-3-methoxy-17-methylmorphinan-6-ol, is an opioid of the morphinan class. Dihydrocodeine and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called a 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.

Dihydrocodeine, along with other morphinans, contains an ether bridge between two of its rings, connecting R4 and R5 through an oxygen group. It also contains a hydroxy group (OH-) bound at R6 and a methyl group located on the nitrogen atom at R17. On the same ring containing the hydroxy group, codeine contains a double bond, which dihydrocodeine lacks. This results in a much more stable chemical structure and also affects its metabolism.

Dihydrocodeine can be synthesized from morphine by reduction of the 7,8-double bond. It readily converts to dihydromorphine with high yields (>95%) which can be methylated to create dihydrocodeine. Dihydrocodeine is analogous to the other morphinans including codeine, heroin, ethylmorphine, hydrocodone, and oxycodone.

Pharmacology

Dihydrocodeine exerts its effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement.

Dihydrocodeine is metabolized via CYP2D6 to the active metabolite dihydromorphine, which has a potency similar to morphine. Other weakly active metabolites include nordihydrocodeine (which is formed via CYP3A4) and dihydrocodeine-6-glucuronide.[3] Although dihydrocodeine does have extremely active metabolites in the form of dihydromorphine and dihydromorphine-6-glucuronide, these metabolites are produced in such a small amount that they do not have clinically important effects.[4]

Binding affinities (Ki)[5]

  • Mu opioid agonist - 325 nM
  • Kappa opioid agonist - 14242 nM
  • Delta opioid agonist - 5905 nM

Dihydrocodeine itself is a weak ligand for the opioid receptors however its main active metabolite - dihydromorphine and one of its metabolites - dihydromorphine-6-O-glucuronide show much stronger agonistic effects.[6]

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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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

Dihydrocodeine has a low toxicity relative to dose. As with all opiates, long-term effects can vary but can include diminished libido, apathy and memory loss. Some people may also have an allergic reaction to dihydrocodeine, such as the swelling of skin and rashes. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.

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

Tolerance and addiction potential

As with other opioids, the chronic use of dihydrocodeine can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of dihydrocodeine 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). Dihydrocodeine presents cross-tolerance with all other opioids, meaning that after the consumption of dihydrocodeine all opioidswill have a reduced effect.

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 dihydrocodeine, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of dihydrocodeine, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of dihydrocodeine 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 dihydrocodeine.

Legal status

  • Austria: Dihydrocodeine is legal for medical use and illegal when sold or possessed without a prescription under the AMG (Arzneimittelgesetz Österreich).[citation needed]
  • Hong Kong - In Hong Kong, dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. A pharmacist can dispense Dihydrocodeine when furnished with a doctors prescription. Anyone who supplies the substance without a prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption, without a licence from the Department of Health, is illegal and carries a $1,000,000 (HKD) fine and/or 7 years imprisonment.
  • Japan - In Japan, dihydrocodeine is available without a prescription; used in cough medicines such as New Bron Solution-ACE. Dihydrocodeine is used as an antitussive in many products as a Dextromethorphan alternative. Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethorphan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase.
  • Switzerland - In Switzerland, dihydrocodeine is legal in limited quantities if the buyer is 18 years or older. After age 30, dihydrocodeine is accessible in unlimited quantities.[citation needed]
  • United Kingdom - In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over-the-counter in small amounts (less than 8 mg), when combined with paracetamol (see co-dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base). Illegal possession of dihydrocodeine can result in up to 5 years in prison and/or an unlimited fine.
  • United States - In the USA, dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine are classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120. The 2013 annual aggregate manufacturing quota is 250 kilos.

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.

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. http://books.google.co.uk/books?id=qoyYobgX0uwC&pg=PA404&lpg=PA404&dq=dihydrocodeine+1908+1911&source=bl&ots=Y7ALb1Yqjo&sig=FIkb3K4UwiXhn8LeO2EzXgxOGQk&hl=en&sa=X&ei=-mq9UsT5J4a10QXT0ID4CQ&ved=0CEQQ6AEwAzgK#v=onepage&q=dihydrocodeine%201908%201911&f=false
  3. Kirkwood LC, Nation RL, Somogyi AA. Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine. Br J Clin Pharmacol. 1997;44:549-55.
  4. The role of active metabolites in dihydrocodeine effects (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/12665158
  5. Affinities of Dihydrocodeine and its Metabolites to Opioid Receptors - Helmut Schmidt et al. (August 2002) | http://onlinelibrary.wiley.com/doi/10.1034/j.1600-0773.2002.910203.x/full
  6. Affinities of Dihydrocodeine and its Metabolites to Opioid Receptors - Helmut Schmidt et al. (August 2002) | http://onlinelibrary.wiley.com/doi/10.1034/j.1600-0773.2002.910203.x/full
  7. Patient Information Leaflet https://www.medicines.org.uk/emc/medicine/18064