Routes of Administration in Medication and Psychedelics

From pills in your palm to droplets under your tongue, medication routes of administration refers to the way you take any drug. “Route” refers to the way a substance enters the body, like an injection or an oral medication.

Routes of administration matter because the way you take a substance can impact how effective it is, how long it lasts, and even the way it makes you feel. That’s a big deal for prescription medications, but it’s also a big deal for psychedelics and the future of psychedelic therapy.

In this article, we’ll provide an overview of routes of administration for medication and talk about how this all relates to psychedelics.

Remember: This information is for educational purposes only. However, we also believe in harm reduction and minimizing the risk associated with psychedelic substances. It’s important to understand the radical differences between administration routes so that people can make informed decisions.

Stay safe, have a sober sitter, and trip responsibly.

Medication Routes of Administration

There isn’t really one “correct” route of drug administration. The way a person takes a substance largely depends on what drug they’re taking.

For example, some drugs don’t work if you take them orally because stomach acid will break them down before they can take effect. Others are too potent to take intravenously and need to be partially broken down through the digestive process in order to achieve a safe dose.

In the case of psychedelic drugs, there are other caveats to consider, like how long a person wants to trip, how intense they want the experience be, and how comfortable they are with the drug itself.

Let’s take a look at the key points people should know about drug administration, then talk about common routes.

Different routes of drug administration

The location a drug is administered determines the medication route of administration. 1 The route depends on the drug effect and profile, as well as other factors like convenience and patient compliance. For example, if it’s difficult to get an IV injection, some drugs might be prescribed as pills instead.

There are many different drug administration routes. The most common routes include the oral route and injections. The major routes are covered below, but it’s worth noting that there are other ways to take a drug, including buccal (tucking the drug inside your cheek), ocular (eye), otic (ear), rectal, and vaginal routes.

8 rights of medication administration

If you know someone who works in healthcare or watch a lot of medical shows, you might have heard of the “five rights” of medication administration to uphold patient safety. 2 These rights have guided medical providers for decades, providing best practices for safe medication administration. 3

More recently, this traditional model has been expanded to include three additional recommendations. Why are we talking about this? If you’re a patient, it’s helpful to understand how healthcare providers minimize the risk of medication error.

The eight rights of medication administration are as follows: 4

Right person: Use at least two identifiers to confirm the patient’s identity.
Right medication: Verify the medication order and label.
Right time: Check the frequency of the medication, when the last dose was given, and confirm you are giving the ordered dose at the correct time.
Right dose: Does the dose match the order? Does it make sense as to the volume of liquid or number of tablets to be taken?
Right route: Is it the correct way to administer the drug, such as oral or sublingual?
Right position: Some medication routes are given with the patient in specific anatomical positions. Is the patient in the right position, such as sitting upright or laying on their side?
Right documentation: Document administration after giving the medication. Chart the time, route, and any other specific information as necessary.
Right to refuse: The patient has the right to refuse medications. Staff has the responsibility to encourage compliance and document refusal.

Some other “rights” include the right reason, which is confirming the rationale for the ordered medication and why the patient is taking it; and the right response, which is making sure the drug leads to the desired effect. 5

Principal medication routes and sites of drug administration

There are many different medication routes and sites of drug administration. Broadly, they can be categorized as enteral and parenteral.

“Enteral” means the drug is taken up by the intestines. This method includes oral, rectal, and siblingual administrations. Bioavailability (that is, how much of the drug your body actually uses) depends on how much of the drug the intestinal tissues absorb.

“Parenteral” refers to any route that is not enteral. Parenteral routes include intravenous (IV) injection, intramuscular (IM) injection, and subcutaneous injections. IV injection is the most common parenteral route. Because IV injections skip digestion, medications that are administered this way are considered 100% bioavailable. 6

Medication administration routes in psychedelic drug research

The routes of administration in psychoactive substances are a little more specialized. In psychedelic drug research, some of the most common routes include various methods of injection and oral administration. 7

As Alaina Jaster notes in Psychedelic Science Review, the way a drug is taken can alter how well it works. For example, LSD is highly potent and easily absorbed when taken orally, under the tongue (sublingual), or between the gum and cheek (buccal). However, DMT is inactive when it’s taken orally, unless it’s combined with MAO inhibitors (as in an ayahuasca brew).

It’s important for researchers to understand how the route of administration can change the drug’s effects. This nuance can help determine the proper route and formulation as psychedelic drugs move through clinical trials.

A note on that last point: If you consider the importance of set and setting, then the way a person takes a drug is critical in terms of providing a sense of comfort and setting them up for a meaningful trip. If someone is expected to get an injection, but they’re uncomfortable with a needle, that can stress them out before their session. Stress can impact a person’s ability to fully let go and approach the experience with a calm, open mind.

Routes and formulations are also important considerations as researchers develop synthetic forms of natural substances. Mother Nature doesn’t really care about consistent doses in natural psychoactive plants—things like season, growing conditions, and harvest time greatly affect potency. But synthetic psychedelic substances are easier to dose accurately. Additionally, synthetic psychedelics help support the conservation of natural flora and fauna.

Conservation is a big deal for a drug like 5-MeO-DMT, which is sometimes harvested from the Sonoran Desert toad. Unfortunately, this practice leads to issues with species conservation and habitat destruction. Similarly, peyote is a controlled plant throughout most of the United States and is a religious sacrament for Indigenous populations. However, it’s at risk of overharvesting because of the increasing popularity of peyote among non-Indigenous people.

In the world of psychedelics, routes of administration that are safe, effective, and consistent open up more possibilities for clinical trials and increased accessibility in the near future.

What is administration of psychedelics, and what are the different routes?

“Administration of psychedelics” is another way of talking about the way that these substances are taken. There isn’t one “best” way to approach these routes; the same drug can have different effects, depending on the way it’s taken.

Generally, the different ways to take psychedelics include:

Oral: Consumed through the mouth. Because the drug goes through the digestive system, the time to onset, drug absorption, and duration are usually longer.
Injection: Some psychedelic drugs can be injected in various means, commonly intravaneous (IV) or intramuscular (IM) injections. These methods tend to be pretty involved because they require extra safety precautions, like sterile equipment and proper skill. This method is used in many psychedelic studies because injections are highly bioavailable.
Sublingual: Absorbed under the tongue. This is a common route of administration for LSD, which can be administered on blotter papers that contain micro amounts of the drug. There’s a large artery under the tongue, and absorbing a substance in this way generally results in faster absorption than consuming it through the mouth. This method also skips digestion.
Inhalation: This method refers to inhaling a gas (like an asthma inhaler). Like sublingual routes of administration, inhaling a drug in this way skips metabolization in the liver because the substance is absorbed through the tissues in the lungs.

How do psychedelic treatments work?

In a clinical setting, such as a hospital or research clinic, treatments are administered in a controlled environment. Generally, after completing preparatory paperwork, questionnaires, and any additional screening procedures in a period leading up to the actual treatment, the patient enters a hospital room or dedicated space to receive the psychedelic. They might be hooked up to machines to monitor vital signs, like heart rate and oxygen levels. From here, the process is pretty similar to receiving any other medication in a hospital setting.

The key element with psychedelic treatments is that they generally combine medication and therapy. There isn’t necessarily a standardized approach to psychedelic treatments, but there are a few common elements:

A medical professional administers a specific dose of a psychedelic drug
The patient is supervised throughout their session
After the session, the integration process helps the patient make sense of the experience, talk about the way it made them feel, and apply any learnings to their daily life

During psychedelic treatment, set and setting are essential. “Set” refers to a person’s mindset, mood, and expectations going into the session. “Setting” refers to not only the environment where the session takes place, but also the person’s relationship with the therapist.

The patient is responsible for bringing a willingness to let go and experience the drug. The therapist is responsible for safely supporting the patient through their trip while maintaining client safety.

It’s worth noting that licensed therapists follow a professional code of ethics that provide guidance and standards of professional conduct. For example, the American Psychological Association states that psychologists do not engage in unfair discrimination, sexual harassment, or exploitative relationships. 8

In an opinion piece published in the Harm Reduction Journal in 2021, the authors proposed a series of questions for clinicians who are considering becoming more involved with psychedelic therapy. 9

For medical professionals, these questions promote productive introspection. For people who are getting to know their therapists, these questions can help a patient decide whether or not the therapist is a good fit.

What are my reasons for doing work that relates to psychedelics?
Am I comfortable with psychedelic content?
What is my level of competency in working with psychedelics and harm reduction? What might I do to develop competency?
What level of risk am I comfortable taking on?
What is my personal level of experience?
What is my privilege and how safe is it for me to practice HRIT (Harm Reduction and Integration Therapy)?
What is my level of support?
Am I interested in policy change?

Why was early therapeutic research on psychedelic drugs abandoned?

In the United States, psychedelic research effectively stopped in the 1970s when Congress passed the Controlled Substances Act. This law classified LSD and other psychedelics as Schedule I drugs: the most restrictive level. It effectively halted new research, ushering in the “dark ages” for psychedelic medicine.

Despite this law, some studies and important touchpoints in psychedelic history persisted after the 1970s. In 1986, Rick Doblin established the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit organization dedicated to psychedelic research for mental health. In 1988, researchers at the Leningrad Regional Center for Alcoholism and Drug Addiction Therapy begin investigating ketamine in the treatment of alcohol and heroin addiction. 10

In 1994, Dr. Rick Strassman became the first person in the United States to examine the effects of psychedelics in humans, after 20 years of stalled research.11 Since then, psychedelic research has expanded dramatically, opening up new avenues for drug development, paths toward legalization, and ongoing studies that examine the intersection of psychedelic therapy and mental health.

The 6 Routes of Psychedelics Administration

In the next section, we’ll look at the ins and outs of six common routes of psychedelics administration. These aren’t the only ways to take psychedelic substances, and it’s important to remember that the route can dramatically change a drug’s effects across different dosages.

Oral route

What is oral administration?

“Oral” refers to taking a drug by mouth, as in a pill, tablet, or beverage.

What are the benefits of oral administration?

Convenient and generally less expensive than other routes 12
Non-invasive and can be self-administered
Generally slower onset and longer duration (although this can be good or bad)

What are the drawbacks of oral administration?

Some psychedelic substances have a bitter, unpleasant flavor
Greater risk of nausea and stomach upset
Drug must be metabolized, which can diminish the concentration of the drug

Intravaneous injection

What is IV administration?

An intravenous injection, also called an IV injection, refers to injecting the drug directly into a vein. A solution containing the drug might be given in a single dose or by continuous IV infusion. 12

What are the benefits of IV administration?

100% bioavailable because it directly enters the bloodstream
Rapid onset because it skips liver metabolization
Ideal for irritating solutions that can’t easily be injected in other ways

What are the drawbacks of IV administration?

Requires sterilized, unused equipment to reduce risk of infection
Substance must be high purity and unadulterated
Requires skill to calculate the dose and safely administer the injection

Intramuscular injection

What is intramuscular injection?

Also called IM, an intramuscular injection involves injecting the drug directly into the muscle.

What are the benefits of intramuscular injection?

Rapid onset
Avoids digestion
Can be administered to different muscles

What are the drawbacks of intramuscular injection?

Often more painful than IV method
Decreased onset and absorption
Requires the use of sterilized equipment and proper skill to administer safely

Topical administration

What is tropical administration?

Topical preparations involve mixing the active drug with an inactive ingredient, which can be placed in ointments, creams, gels, and other products that are applied to the skin or mucous membranes of the eye, ear, nose, etc.

What are the benefits of topical administration?

Requires minimal skill to administer
Skips GI tract digestion

What are the drawbacks of topical administration?

Less common than other routes, so options are limited
Ideal for localized effects, but not necessarily for systemic effects

Which psychedelics are best administered topically?

At this point, it’s too early to say—but that might change rapidly in the next few years. Right now, topical cannabinoids dominate the market with CBD balms and THC-infused creams. At least one company is working on topical applications for psychedelics: According to the website, “Psycheutical’s patented NeuroDirect™ delivery technology delivers neuro-active compounds directly into the nerve tissue via topical application at the back of the neck.”

Sublingual administration

What is sublingual administration?

This refers to drugs that are absorbed under the tongue. There’s a large artery under the tongue, and applying the drug to this location allows the drug to passively diffuse into the bloodstream.

What are the benefits of sublingual administration?

Skips digestion
Faster absorption than oral route
Ideal for drugs that would be destroyed or inactivated in the stomach

What are the drawbacks of sublingual administration?

Certain drugs can irritate tissues in the mouth
Some substances have a bitter flavor

Inhalation

What is inhalation?

In psychedelics, inhalation is used for gases that enter the bloodstream by diffusing across the tissues in the lungs. This method is also called the pulmonary route.

What are the benefits of inhalation?

Rapid onset
Localized effects

What are the drawbacks of inhalation?

Frequent inhalation can damage mucous membranes in the nose
Sharing equipment can increase risk of infection
Requires proper inhalation technique

Things to Know

Routes of administration: The way a drug is administered can change its effect, onset, and duration. There are many different ways to administer a drug. The “best” route depends on what’s best for the patient, the drug they’re taking, and what their provider prescribes.

8 rights of medication administration:

Right person
Right medication
Right time
Right dose
Right route
Right position
Right documentation
Right to refuse

The 6 routes of psychedelics administration:

Oral: Administered by mouth
Intravenous (IV): Injected by syringe directly into the bloodstream
Intramuscular (IM): Injected by syringe directly into the muscle
Topical: The active drug is combined with an inactive ingredient and applied as a lotion, ointment, gel, or other formulation
Sublingual: Absorbed under the tongue
Inhalation: Inhaled as a gas

Medication administration in psychedelic research: There are many ways to administer psychedelic drugs. Injections are commonly used to ensure accurate dosage and delivery. However, other routes are being examined as psychedelic drug research continues to evolve, such as oral and topical routes, which may make these substances more accessible in the future.

The Bottom Line

The way a drug is taken matters just as much as the drug itself. This topic is an important point for psychedelic substances because the way a person feels can dramatically affect the course of their psychedelic experience. Providing a person with a simple, familiar way to take a psychoactive substance (like a pill) can help them feel more comfortable with the treatment as a whole.