Routes of administration

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See also: Dosage form

A route of administration is the method in which a psychoactive substance is delivered into the body.

The route through which a substance is administered can greatly impact its potency, duration, and subjective effects. For example, many substances are more effective when consumed using particular routes of administration, while some substances are completely inactive with certain routes.

Determining an optimal route of administration is highly dependent on the substance consumed, its desired duration and potency and side effects, and one's personal comfort level.

Oral cavity

It is worth noting that most substances are reported to be strongly bitter and unpleasant to administer via sublingual or buccal routes.

Oral

Oral administration is the most common route of administration for most substance classes. This route allows a substance to be absorbed through blood vessels lining the stomach and intestines. The onset is generally slower than other methods of ingestion as it must undergo first-pass metabolism through the liver (may vary greatly between individual substances).[1] Additionally, the absorption and overall duration are generally longer as well.

Risks

This method can also have a greater propensity for nausea and gastrointestinal discomfort.[2][3]

Sublingual

Sublingual administration refers to absorption under the tongue.[4] It is a common route of administration for lysergamides like LSD.

This route causes the substance to be absorbed through the large lingual artery present underneath the tongue, generally resulting in a faster absorption than oral administration.

It also circumvents first-pass metabolism of certain substances which can be absorbed via sublingual and buccal administration but not oral administration (e.g. 25x-NBOMe, 25x-NBOH).

Risks

Caustic compounds, such as the freebase form of amine-containing substance, should not be used sublingually because they can severely burn the inside of one's mouth.

Buccal

Buccal administration refers to absorption through the cheek and gum.

This route is commonly employed when ingesting potent psychedelics such as 25I-NBOMe, DOM, LSD, and other substances distributed on blotter paper. Potent clandestine manufactured benzodiazepines like alprazolam and etizolam are also sometimes distributed on blotters.

Like sublingual absorption, the substance is largely absorbed through the lingual artery, but is also absorbed through the gum lining. This method is used when chewing plant leaves such as khat, kratom, salvia divinorum, and sometimes tobacco (snus).

Nasal cavity

Skull and crossbones darktextred2.png

SARS-CoV-2: drug use safety considerations

Avoid sharing drug paraphernalina for insufflation (straws, bank notes, ‘Kuripe’, etc).


Nasal spray

Actuation of a nasal spray bottle, used to deliver medication via the nostrils

"The administration of nasal powder formulations has been associated with greater sensory irritation than liquid sprays and the amount of powder.".[5]

To learn how to make nasal spray, see the nasal spray guide.

Insufflation

Insufflation (also called "inhalation" and "snorting") refers to the introduction of a substance into the sinus via the nostrils, circumventing first pass metabolism.

It is a very common method of use for substances in powder form, specifically so-called "street drugs" like cocaine, heroin, and methamphetamine. Some users find this route to be painful and uncomfortable, although certain substances are easier to insufflate than others.

This method is capable of rapid absorption through mucous membranes and blood vessels in the sinus. Absorption and onset is generally much more rapid than oral and, as a result, a substance feels much more intense and is often shorter acting than if taken orally.

Insufflation is common with substances such as cocaine and ketamine. It is also utilized in yopo rituals, the self-applicator pipe is known as ‘Kuripe’, and the blow pipe is known as a ‘Tepi’ in the Brazilian tradition. Insufflating tobacco in snuff form was a common practice until the early 20th century.[citation needed]

Risks

Short-term side effects of insufflation includes nasal congestion, which may last for 24 hours.

Frequent insufflation of some substances can damage one's mucous membranes, induce bleeding, damage the nostril's cartilage and lining, burn the throat, and cause other trauma to the nasal passage and sinus area.[6] To reduce damage, it is recommended to grind the substance completely before use and alternate nostrils.[7]

Also, sharing snorting equipment (straws, banknotes, bullets, etc) has been linked to the transmission of hepatitis C. (Bonkovsky and Mehta) In one study, the University of Tennessee Medical Center researches warned that other blood-borne diseases such as HIV, the AIDS-causing virus, could be transmitted as well.[8]

Respiratory tract

Skull and crossbones darktextred2.png

SARS-CoV-2: drug use safety considerations

Avoid sharing drug paraphernalina for inhalation (vapes, joints, pipes, etc).

Inhalation

Inhaled administration is used for inhalants gases such as nitrous oxide, volatile liquids such as ether, and volatile viscous compounds such as poppers.

Inhalants do not require an external heat source to produce psychoactive vapors that can then be inhaled through various methods depending on the substance used. Inhaled substances are absorbed very rapidly and lead to an almost instantaneous absorption of the substance and passage through the blood brain barrier.[9]

Risks

It is substantially easier to overdose on alcohol inhalation than drinking alcohol.

Many substances can be inhaled to achieve an altered state of consciousness, however, some substances used for this purpose produce highly negative physical and neurotoxic effects including solvents like toluene (see toluene toxicity) often found in glue, acetone often found in nail polish, and gasoline.[10], and number of gases intended for household or industrial use including butane gas sold as lighter gas refill.

Inhaling liquified gas directly from cans or canisters can freeze the throat.

Heating

In order for cocaine (in plastic bag at bottom) to be converted to crack, several supplies are needed. Pictured here are baking soda (a commonly used base in making crack) a metal spoon, a tea light, and a cigarette lighter. The spoon is held over the heat source in order to "cook" the cocaine into crack.

Substances that come in HCl form can be converted to freebase by mean of pH regulation. For example, cocaine decomposes when heated strongly so the freebase and hydrogen carbonate salts of cocaine, which have much lower boiling points compared to the hydrochloride salt, are typically used when the substance is to be vaporized and are known as cocaine base and "crack" respectively.

Other substances decomposes to easily even from low heat so they cannot even be vaporized for this reason. Examples of substances include amphetamine, caffeine, LSD, and psilocybin. Also, there's not a single trip report in PiHKAL (“Phenethylamines I Have Known and Loved”) in which the subject is smoking or vaporizing the phenethylamine compound. Notable compunds in PiHKAL include MDMA, and the “Magical half-dozen” (mescaline, DOM, 2C-B, 2C-E, 2C-T-2, 2C-T-7). However, a substituted phenethylamine that was synthesized after PiHKAL was released albeit very toxic, 25I-NBOMe, has been smoked.[11]

Smoked

Smoking substances is a common method of consumption with the most common examples including cannabis and tobacco. Smoking yeilds low bioavailability, especially if the substance is smoked slowly.

To smoke a substance a direct heat source, most often a flame, is applied directly to the substance with no barrier between the heat source and the substance. The smoking of substances can lead to an almost instantaneous absorption of the substance and passage through the blood brain barrier.[1]

When a substance is smoked, the substance is absorbed through blood vessels found in the bronchi tubes contained within the lungs. Like insufflation, the duration is decreased while its intensity is increased in proportion to oral absorption. Smoking a substance also bypasses the GI tract's tendency to break certain substances down, such as DMT.

Cannabis is commonly consumed via the respiratory tract. The average THC transfer rate for joints, bongs, and vaporizers, is 20-26%,[12] 40%,[12] and 55-83%,[13] respectively. For a proper gas or smoke deposition, one are advised to take a deep initial breath, and then hold it for 10 seconds to allow for the gas or smoke to get fully absorbed in the lungs. Subjects are frequently instructed to follow the "10 seconds rule" in studies.[14][15] Prolonged breath holding does not substantially enhance the effects of inhaled marijuana smoke.[16][17]

Bongs that are cleaned regularly eliminates yeast, fungi, bacteria and pathogens that can cause several symptoms that vary from allergy to lung infection.[18][19][20]

Vaporized

Vaporizing substances is a common method of consumption with the most common examples including cannabis and nicotine, but also heroin and crack-cocaine. Vaporizing a substance, especially with a digital temperature controlled device, allows for more temperature control because the flame or heat source does not come into direct contact with the substance.

Even though many drugs, like heroin and oxycodone pills are colloquially referred to as "smoked" the process used to consume them is vaporization. Vaporizing substances can lead to an almost instantaneous absorption of the substance and passage through the blood brain barrier.[1]

When a substance is vaporized, the substance is absorbed through blood vessels found in the bronchi tubes contained within the lungs. Like insufflation, the duration is decreased while its intensity is increased in proportion to oral absorption. Vaporizing a substance also bypasses the GI tract's tendency to break certain substances down, such as DMT.

Vaporization is commonly associated with the vaporizer pens that have become popular within the past decade, but it is not limited to ingesting the vapors from an electronic heat source.

Risks

Smoking a substance that should be vaporized leads to a blast of heat that may burn off the active ingredient or ignite the substance itself, both of which are wasteful and incorrect, which may cause judgement impairment of the dosage.

Ethnobotanist Daniel Siebert cautions that inhaling hot air can be irritating and potentially damaging to the lungs. Vapor produced by a heat gun needs to be cooled by running it through a water pipe or cooling chamber before inhalation.[21]

Re-used uncleaned vapes, and vape sharing, may cause bacterial pneumonia[22][23] fungal pneumonia,[24], and viral pneumonia.[22]

E-cigarette

An electronic cigarette is an electronic device that simulates tobacco smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such, using an e-cigarette is often called "vaping". The atomizer is a heating element that vaporizes a liquid solution called e-liquid. The most common e-liquid carrying agents includes glycerin (often called vegetable glycerin, or VG), and propylene glycol (often referred to as PG).

Risks

Vaping-associated pulmonary injury (VAPI) is an umbrella term used to describe lung diseases associated with the use of vaping products that can be severe and life-threatening.

Glycerin was long thought to be a safe option. However, the carcinogen formaldehyde is known as a product of propylene glycol and glycerol vapor degradation.[25]

The Machine

The Machine, utilizing a glass bottle with a hole, and foil in the neck. The Machine was invented to make it more convenient to smoke DMT, but it can be used for any substance.

Gravity bong

See Gravity bong (Wikipedia)

  • Diagram of bucket bong in operation

  • Diagram of waterfall bong in operation

Chasing the dragon

Chasing the dragon, aka foily.

Heroin is colloquially referred to as "smoked" but is really vaporized, often using tinfoil as a barrier between the substance and the flame source. The heat source can be held at different distances as temperature control. An alternative version is to use a "stainless steel one-quarter teaspoon and vaporized it over a cigarette lighter collecting the smoke in an upside-down funnel."[26]

Risks

This is likely the least clinically delivered route of administration. An overdose caused by chasing the dragon is hard to predict because this technique doesn't deliver a standardized dosage. It's virtually impossible even for skilled users to know how much of the substance that has been evaporated, burned, and inhaled.

These combined factors may create a false sense of security when a given dose seems safe to repeat, but may cause an overdose when all the factors are randomly excluded.

#The Machine is a much safer than chasing the dragon.

Injection

A diagram showing the different angles needed for different types of injections

Some drugs cannot be taken injected: For example, injectable codeine is available for subcutaneous or intramuscular injection only; intravenous injection is contraindicated as this can result in non-immune mast-cell degranulation and resulting anaphylactoid reaction.

About 0.1 mL of the solution is lost in conventional syringes through the Luer taper tip and the Luer taper adapter of the hypodermic needle. That can be compensated by either adding extra 10% or 5% substance in 1 mL or 2 mL syringes respectively, or by using low dead space syringes.

Intravenous

Main article: Safer injection guide § IV injection

Intravenous administration refers to a drug being directly introduced into the bloodstream using a hypodermic needle. This method has the benefit of a very short onset and eliminates absorption by directly entering the bloodstream.[1] However, much greater care must be taken when compared to other methods of administration.

Sterilized, unused needles and a high purity substance with little to no adulterant are required to avoid damage to the circulatory system.[27]

Make sure no air bubbles are present in the reservoir before the plunger is released. Hold the syringe vertically and flick it with your fingers to release bubbles to the needle adapter, and gently push the plunger. Don't worry about air embolism, it is estimated that a large volume of 50-500 mL or greater infused at a rapid rate is potentially fatal.[28][29]

This route is strongly associated with substances that have bad oral bioavailability, such as heroin and cocaine, but can be employed with almost any pure substance.

Intramuscular

Main article: Safer injection guide § IM injection

Intramuscular administration refers to a drug being injected into the muscle tissue using a hypodermic needle. This method is very similar to the intravenous route, but is often more painful with a decreased onset and absorption. Some drugs (such as ketamine that has low oral bioavailability, and is dangerous to take intravenously rapidly) are commonly administered via this route.[30] Like intravenous administration, intramuscular injection must be taken with precaution, using sterilized unused needles.

Subcutaneous

Main article: Safer injection guide § SC injection

Subcutaneous administration (also known as skin popping) refers to a drug being injected into the subcutis, the layer of skin directly below the dermis and epidermis. Subcutaneous administration is relatively uncommon among psychonautics, as many people are not trained how to do it or would rather use a different route of administration which they are more familiar with.

Rectal

Rectal administration, also commonly referred to as boofing or plugging, is one of the most effective methods of administration for many substances.[31][4] The absorption rate is very high compared to other methods and the onset is usually very short, generally with a higher intensity and shorter duration.

This is due to a large amount of arteries located in the rectum; thus rectal administration is often superior to other methods despite social stigma.

Rectal administration can involve either the insertion of a low-volume solution into the rectum, using a syringe or pipette, or by placing a pill or gelatin capsule containing the active substance. The latter form is known as a suppository, and is common in medicine when the gastrointestinal tract cannot support oral medicine.

Risks

Caustic substances such as 4-FA or phenibut hydrochloride should not be plugged because they can burn the interior rectum resulting in a considerable amount of gastrointestinal distress.

Transdermal

Transdermal is a route of administration where active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery for opioids such as fentanyl [32] and transdermal implants used for medical or anesthetic purposes. This route is typically not observed in non-medical or recreational contexts due to the manufacturing requirements.

See also

External links

References

  1. ↑ 1.0 1.1 1.2 1.3 Ohlsson, A., Lindgren, J.-E., Wahlen, A., Agurell, S., Hollister, L. E., Gillespie, H. K. (September 1980). "Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking". Clinical Pharmacology and Therapeutics. 28 (3): 409–416. doi:10.1038/clpt.1980.181. ISSN 0009-9236. 
  2. ↑ Niv, D., Davidovich, S., Geller, E., Urca, G. (December 1988). "Analgesic and hyperalgesic effects of midazolam: dependence on route of administration". Anesthesia and Analgesia. 67 (12): 1169–1173. ISSN 0003-2999. 
  3. ↑ Porter, W. R., Intraoral methods of using benzodiazepines 
  4. ↑ 4.0 4.1 De Boer, A. G., De Leede, L. G. J., Breimer, D. D. (January 1984). "DRUG ABSORPTION BY SUBLINGUAL AND RECTAL ROUTES". British Journal of Anaesthesia. 56 (1): 69–82. doi:10.1093/bja/56.1.69. ISSN 0007-0912. 
  5. ↑ https://pubmed.ncbi.nlm.nih.gov/35386013/
  6. ↑ Ask Erowid : ID 41 : Is snorting MDMA worse for you than taking it orally? 
  7. ↑ Research chemicals (MyCrew) http://www.mycrew.org.uk/drugs-information/research-chemicals
  8. ↑ Sharing Drug “Snorting Straws” Spreads Hepatitis C, 2016 
  9. ↑ http://www.ct.gov/dds/lib/dds/edsupp/medadmin_recert_part_ii.pdf
  10. ↑ Burbacher, T. M. (December 1993). "Neurotoxic effects of gasoline and gasoline constituents". Environmental Health Perspectives. 101 (Suppl 6): 133–141. ISSN 0091-6765. 
  11. ↑ "2C-I-NBOMe (25I) Effects". Erowid. 
  12. ↑ 12.0 12.1 https://www.ukcia.org/research/FactorsThatInfluenceBioavailability.pdf
  13. ↑ Lanz, C., Mattsson, J., Soydaner, U., Brenneisen, R. (19 January 2016). "Medicinal Cannabis: In Vitro Validation of Vaporizers for the Smoke-Free Inhalation of Cannabis". PLoS ONE. 11 (1): e0147286. doi:10.1371/journal.pone.0147286. ISSN 1932-6203. 
  14. ↑ Wallace, M. S., Marcotte, T. D., Umlauf, A., Gouaux, B., Atkinson, J. H. (July 2015). "Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy". The journal of pain : official journal of the American Pain Society. 16 (7): 616–627. doi:10.1016/j.jpain.2015.03.008. ISSN 1526-5900. 
  15. ↑ Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J., Bentley, H., Gouaux, B., Fishman, S. (June 2008). "A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain". The journal of pain : official journal of the American Pain Society. 9 (6): 506–521. doi:10.1016/j.jpain.2007.12.010. ISSN 1526-5900. 
  16. ↑ Zacny, J. P., Chait, L. D. (1991). "Response to marijuana as a function of potency and breathhold duration". Psychopharmacology. 103 (2): 223–226. doi:10.1007/BF02244207. ISSN 0033-3158. 
  17. ↑ Zacny, J. P., Chait, L. D. (June 1989). "Breathhold duration and response to marijuana smoke". Pharmacology, Biochemistry, and Behavior. 33 (2): 481–484. doi:10.1016/0091-3057(89)90534-0. ISSN 0091-3057. 
  18. ↑ Can You Get Sick From Dirty Bong Water? 
  19. ↑ https://www.maryjanetokes.com/dirty-bong-the-dangers-of-using-one/
  20. ↑ The Dangers of a Dirty Bong, 2018 
  21. ↑ Ask Erowid : ID 3139 : Do vaporizers work with Salvia divinorum? 
  22. ↑ 22.0 22.1 Kooragayalu, S; El-Zarif, S; Jariwala, S. doi:10.1016/j.rmcr.2020.100997. PMC 6997893 Freely accessible. PMID 32042584 //www.ncbi.nlm.nih.gov/pmc/articles/PMC6997893.  Missing or empty |title= (help)
  23. ↑ "Vaping changes oral microbiome and raises infection risk". www.medicalnewstoday.com (in English). 14 March 2020. 
  24. ↑ Mughal, Mohsin Sheraz; Dalmacion, Denise Lauren V.; Mirza, Hasan Mahmood; Kaur, Ikwinder Preet; Dela Cruz, Maria Amanda; Kramer, Violet E. (1 January 2020). "E-cigarette or vaping product use associated lung injury, (EVALI) - A diagnosis of exclusion". Respiratory Medicine Case Reports (in English). p. 101174. doi:10.1016/j.rmcr.2020.101174. 
  25. ↑ Lestari, Kusuma S.; Humairo, Mika Vernicia; Agustina, Ukik (July 11, 2018). "Formaldehyde Vapor Concentration in Electronic Cigarettes and Health Complaints of Electronic Cigarettes Smokers in Indonesia". Journal of Environmental and Public Health. 2018: 1–6. doi:10.1155/2018/9013430 Freely accessible. ISSN 1687-9805. PMC 6076960 Freely accessible. PMID 30105059. 
  26. ↑ "Erowid Online Books : "TIHKAL" - #38 5-MEO-DMT". www.erowid.org. 
  27. ↑ Evans, S. M., Cone, E. J., Henningfield, J. E. (1 December 1996). "Arterial and venous cocaine plasma concentrations in humans: relationship to route of administration, cardiovascular effects and subjective effects". Journal of Pharmacology and Experimental Therapeutics. 279 (3): 1345–1356. ISSN 0022-3565. 
  28. ↑ http://www.ajol.info/index.php/sajr/article/viewFile/34461/6388.  Missing or empty |title= (help)
  29. ↑ Gordy S, Rowell S (January 2013). "Vascular air embolism". International Journal of Critical Illness and Injury Science. 3 (1): 73–76. doi:10.4103/2229-5151.109428. PMC 3665124 Freely accessible. PMID 23724390. 
  30. ↑ Craven, R. (December 2007). "Ketamine". Anaesthesia. 62 (s1): 48–53. doi:10.1111/j.1365-2044.2007.05298.x. ISSN 0003-2409. 
  31. ↑ Aungst, B. J., Rogers, N. J., Shefter, E. (1 January 1988). "Comparison of nasal, rectal, buccal, sublingual and intramuscular insulin efficacy and the effects of a bile salt absorption promoter". Journal of Pharmacology and Experimental Therapeutics. 244 (1): 23–27. ISSN 0022-3565. 
  32. ↑ Fentanyl Transdermal Patch: MedlinePlus Drug Information 
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