Chronic Marijuana Use May Increase Sedation Needs

Jason R. Flores, DDS, MHA, RN


Cannabis has become a mainstay in 33 states for medical use and 11 states for recreational use. As chronic marijuana use becomes more acceptable, sedation patterns for outpatient procedures, including dental treatment, have changed to include an overwhelming increase in the needs for some sedatives.

This article examines the patterns of use for increased levels of propofol via the pharmacokinetics of cannabis and propofol in a cannabis consumer, explaining why the increases in propofol are occurring and recognizing that increasing propofol levels may be needed to maintain sedation.

Where increased propofol levels may not be an option, as it decreases the margin of safety, the dentist may need to modify the sedation. This article explores what receptors need to be avoided in sedation modification as well as some drug classes that are available.


Depending what time period was “your decade,” cannabis may have been the “devil’s weed,” “reefer,” “Mary Jane,” “ganja,” or “pot.” Societal taboos of abuses have diminished, and current medical outlooks on cannabis uses are now mainstream. Even the stuffiest medical institutions are looking for new and inventive ways to use it.

For example, tetrahydrocannabinol (THC) is being used to treat children and adults in disease processes ranging from pain, inflammation, and spasticity to asthma, obstructive sleep apnea, and psychiatric disorders.   

Medical uses of cannabis have been remarkably broad. Patients report relief from a lifetime of ailments, and sometimes just as exhausting treatments, in a matter of months with THC use. THC is one of more than 400 chemical compounds that constitutes cannabis, and it is the main psychotropic component.1

The most common daily dosage is 20 to 30 mgs orally, divided into two or three doses of 10 to 15 mgs, with tolerance beginning at greater than 30 mgs/day.2 The patterns and length of marijuana use varies greatly among users and mainly depend on the desired patient affect.

For users seeking the psychotropic affects, Bahorik, Leibowitz, et al, reported that the mean usage pattern was an increasing dosage for the first six months, up to 30 mgs/day, with a majority of the patient population being 50 years old and older.3 After the first six months, the dosages leveled out, with a duration of reported use of 30 years.3

For patients seeking to achieve the anti-inflammatory effect of THC, the user profile was younger, with the mean age being 33, and dosages of 2.5 mgs, two or three times daily.2,4 Patients reported use of a few months to less than 10 years.4

For the purpose of this article, THC and cannabis will be used interchangeably. This article is not to echo the wonders of THC, and the idea that marijuana affects sedation is not new. Clinically, most in the anesthesia community are well-versed in handling patients such as those presented.

This article focuses more on the complex interactions with THC and endogenous neurotransmitters in an attempt to explain biochemically what is happening inside of our patients, through accurate and through literature review. It will present four documented cases to recount subjective events that led to this in-depth literary review.

These specific cases were selected for their matching qualities, with the exception of use of cannabis. This article seeks to clarify the relationship between the observed anecdotal effects witnessed in this patient population and peer-reviewed scientific literature of the internal pharmacologic activity.

A Colorado-based research team reviewed charts for gastric outpatient procedures at an outpatient clinic. For April 2019, regular cannabis consumers needed 14% more fentanyl, nearly 20% more midazolam, and 220.5% more propofol to achieve adequate sedation levels equivalent to sedation in non-marijuana patients.5

In this study, regular use was defined as daily marijuana use, and all of the subjects tested showed the need for increased sedation medications.5 Medical histories beyond the gastrointestinal procedures performed were not reported.

Comparably, when I have performed anesthesia/sedations in the outpatient dental, oral, and maxillofacial surgical center, I have noted the same need for increased sedatives, most notably the dramatic increase in propofol.

In my review of only my intravenous (IV) sedation cases for the past 12-month period, about 600 IV cases, non-cannabis patients on average used 25 to 30 mgs of propofol administered prior to and during local injections either by infusion or divided bolus doses, with the propofol infusion pump administering at 50 mcgs/kgs/min throughout the 60- to 90-minute cases. At this infusion pump dose, non-cannabis patients are complacent with intraoral injections and extractions. This was a commonality among most all non-cannabis patients.

But reviewing the charts for daily cannabis consuming patients, about 100 cases, revealed that 100 to 150 mgs infused or bolused in divided doses prior to and during local injections for cannabis consumers was routine, with the propofol infusion pump administering at 90 to 110 mcgs/kgs/min throughout the 60- to 90-minute cases. Often times, the cannabis consumer is still able to coherently verbalize the desire for more sedative.

Case 1

A 23-year-old female weighing 55 kgs requested IV sedation for extraction of teeth No. 1 (erupted), 16 (impacted), 17 (impacted), and 32 (partially erupted). Her medical history noted daily use of cannabis due to chronic abdominal pain caused by endometriosis.

The patient had a medical marijuana prescription, and the only other medication reported was ethinyl estradiol-levonorgestre, an extended cycle birth control pill to offset the damaging effects of endometriosis.

The patient reported oral THC use for the previous five years, daily with 10 mgs at noon and 20 mgs at bedtime. Prior to her marijuana card, she smoked marijuana daily at a rate of one to three joints depending on whether it was a weekday or weekend for two years.

On the day of the dental surgery, a 22-g IV was inserted in the right dorsal metacarpal vein in the dental surgical center’s preoperative area. The patient was forthcoming that she did not adhere to instruction of cannabis cessation two weeks prior to dental surgery and had “smoked a bowl” the previous night, with a “hit” that morning around two hours prior to her arrival at the surgical center.

Two milligrams of midazolam were administered before we escorted her to the operating room via stretcher. After transferring her to the dental operating chair, a three-lead EKG, pulse oximeter, blood pressure cuff, nasal cannula with 2-L oxygen flow, protective goggles, protective arm restraints, and precordial stethoscope were placed on the patient.

While the dental surgical team washed, 2 mgs of midazolam, 25 mcgs of fentanyl, and 10 mgs of propofol were bolused, and propofol was started via infusion pump at 50 mcgs/kgs/min. Surgeons gowned, timeout was performed, and immediately prior to local anesthesia administration, an additional 2 mgs of midazolam, 25 mcgs of fentanyl, and 10 mgs of propofol were bolused, and propofol infusion was increased to 60 mcgs/kgs/min. Respirations via precordial were 20 breaths/min.

The patient immediately exhibited vocal and physical distress to the intraoral injections, yelling and breaking free from the protective restraints, requiring the registered nurse in the OR to physically restrain the patient’s limbs to protect her and the surgical team. The patient did not exhibit any signs of disorientation, and instead started clearly vocalizing that she was “not asleep at all.”

An additional 20 mgs of propofol, 1 mg versed, and 25 mcgs of fentanyl were bolused. The propofol infusion was increased to 80 mcgs/kgs/min. The patient calmed to the pausing of the intraoral injections and clearly verbalized the desire for more medications. An additional 20 mgs of propofol were administered.

Upon resuming the intraoral injections, the patient began wildly flailing her limbs again, began spitting the dental mouth molt out of her mouth, and verbalized her dissatisfaction with “being awake.” An additional 20 mgs of propofol, 2 mgs versed, and 25 mcgs of fentanyl were administered, with the propofol infusion increased to 100 mcgs/kgs/min.

The patient calmed enough to endure the intraoral injections, but with the introduction of pressure to the area of tooth No. 1, she began to flail her head and wail. At the point of patient agitation, the blood pressure remained within 10% of baseline at 87 bpm, and blood pressure was recorded as 130/84. Both vital sign parameters are not indicative of a pain response, but an additional 1.7 mls of 2% lidocaine with 1:100,000 epinephrine was administered in the area of tooth No. 1.

After an appropriate pause for local penetration, the surgical assistant held the paient’s head still and began comforting verbal commands to stay immobile. The dental surgical resident successfully extracted tooth No. 1, with the patient still struggling against the pressure. The dental anesthesiologist increased the propofol infusion to 110 mcgs/kgs/min and administered 50 mgs of diphenhydramine and 2 mgs versed.

The second extraction was equally as disruptive, especially as the surgical handpiece was introduced to remove bone, and additional local anesthetic was applied to the area of tooth No. 32. The remaining extractions were equally stressful to the patient, despite additional sedative and local injection dosing.

The patient never achieved expected levels of deep sedation despite a total of 454 mgs of propofol, 12 mgs versed, 100 mcgs of fentanyl, 30 mgs of toradol, and 50 mgs of diphenhydramine. Although of note, after the dosing with 50 mgs of diphenhydramine, the patient calmed considerably, including decreases in vocalizations due to discomfort.

Case 2                                               

A 23-year-old female who weighed 58 kgs requested IV sedation for the extraction of teeth No. 1 (erupted), 16 (erupted), 17 (impacted), and 32 (impacted). She denied any cannabis use in her documented medical history.

On the day of the dental surgery, a 22-g IV was inserted in the right antecubital vein in the preoperative bay. Two milligrams of midazolam were administered before she was escorted to the operating room via stretcher. After transfer to the dental operating chair, a three-lead EKG, pulse oximeter, blood pressure cuff, nasal cannula with 2-L oxygen flow, protective goggles, protective arm restraints, and precordial stethoscope were placed on the patient.

While the dental surgical team washed, 1 mg of midazolam, 25 mcgs of fentanyl, and 10 mgs of propofol were bolused, and propofol was started via infusion pump at 50 mcgs/kgs/min. Surgeons gowned, and timeout was performed. Immediately prior to local anesthesia administration, an additional 2 mgs of midazolam, 25 mcgs of fentanyl, and 10 mgs of propofol were bolused, and propofol infusion increased to 60 mcgs/kgs/min.

Light snoring was noted with periodic obstruction heard through the precordial. As the resident moved to inject the other half of the mouth, an additional 2 mgs of midazolam and 25 mcgs of fentanyl was given to maintain a deep level of sedation. The patient did not respond to injection stimulus, and no more boluses were given during extractions of the first three third molars.

Precordial respirations were 14 min, and propofol infusion was decreased to 50 mcgs/kgs/min after tooth No. 1 was extracted. After the extraction of tooth No. 16 and surgical extraction of tooth No. 17, breathing was quiet and controlled at 16 breaths/min, with minimal movement from the patient.

After surgical extraction of tooth No. 32, propofol infusion was decreased to 40 mcgs/kgs/min, with an additional 1 mg of midazolam and the remaining 25 mcgs of fentanyl given. Propofol infusion was discontinued as the last socket was sutured.

Total drug administration was 8 mgs of midazolam, 100 mcgs of fentanyl, and 210 mgs of propofol over an approximately 60- to 70-minute procedure. The patient recovered well and never expressed signs of distress.

Case 3

A 28-year-old male weighing 67 kgs was seen for extractions of teeth No. 1 (impacted), 17 (soft tissue, partially impacted), 32 (erupted), and 16 (congenitally missing). He requested IV sedation. His medical history revealed daily cannabis prescriptive use due to autism spectral disorder.

The patient also reported oral THC use for the previous three years daily with no use in the morning, 5 mgs when arriving at home after work, around 4 pm, and 10 mgs at bedtime. Prior to his marijuana card, he smoked marijuana on weekend nights only at a rate of one joint on Friday and one joint on Saturday. The only other medication listed for this patient was occasional use of omeprazole when needed.

A 22-g IV was placed in the right antecubital vein in the preoperative area, and 2 mgs of midazolam were administered prior to stretcher transport to the operating room. The same patient monitoring and protective procedures were repeated in this case as in Case 1 and 2.

While the surgical attending and resident scrubbed, 2 mgs of midazolam and 25 mcgs of fentanyl were bolused. As surgeons gowned, 10 mgs of propofol, 1 mg of midazolam, and 25 mcgs of fentanyl were bolused, and propofol infusion was set at 50 mcgs/kgs/min.

The patient was appropriately responsive to verbal commands for the beginning of intraoral local injections and requested more sedation. The oral surgeon (OMFS) performing the case also requested a deeper level of sedation for the patient. An additional 2 mgs versed, 25 mcgs of fentanyl, and 10 mgs of propofol were bolused, and propofol infusion was increased to 80 mcgs/kgs/min.

The patient appeared to be calm but began displaying signs of distress upon tissue manipulation, with clear verbalization that he was “not asleep.” The OMFS asked if pain was being experienced, and the patient answered “no.”

To ensure profound localization, the OMFS reapplied additional local anesthesia to the extraction area, and an additional 1 mg of midazolam, 10 mgs of propofol bolus, and 25 mcgs of fentanyl were given. The dental anesthesiologist, having benefited in the past from IV diphenhydramine, administered 50 mgs of diphenhydramine.

As the OMFS began the extraction of tooth No. 1, the patient began to aggressively fight against the safety bands, shake his head, and cry out loudly. The mouth prop was removed. The patient was coherent and asked to be “given more stuff.” The OMFS asked again if the patient was experiencing pain. The patient stated he was not experiencing pain, but expected to be “more asleep.”

Next, 20 mgs of propofol and 2 mgs versed were bolused, and propofol infusion was increased to 120 mcgs/kgs/min. The patient was instructed to keep his arms down and stop moving his head. As in Case 1, the remaining extractions were equally as unruly, especially as the surgical handpiece was introduced to remove bone. The remaining extractions were equally stressful to the patient, despite additional sedative and local injection dosing.

As with Case 1, the patient never achieved expected levels of deep sedation despite a total of 487 mgs of propofol, 10 mgs versed, 100 mcgs of fentanyl, 30 mgs of toradol, and 50 mgs of  diphenhydramine. And as with Case 1, after the dosing with 50 mgs of diphenhydramine, the patient calmed considerably, although he never achieved deep sedation levels.

Case 4

A 31-year-old male weighing 72 kgs was seen for extractions of teeth No. 1 (erupted), 16 (partially erupted), 17 (impacted), and 32 (partially erupted). The patient requested IV sedation. His medical history stated no cannabis use or history.

A 22-g IV was placed in the right antecubital vein in the preoperative area, and 2 mgs of midazolam were administered prior to stretcher transport to the operating room. The same patient monitoring and protective procedures were repeated in this case as in previous cases.

While the surgical attending and resident scrubbed, 2 mgs of midazolam, 10 mgs of propofol, and 25 mcgs of fentanyl were bolused. As surgeons gowned, 10 mgs of propofol, 1 mg of midazolam, and 25 mcgs of fentanyl were bolused, and propofol infusion was set at 50 mcgs/kgs/min.

The patient was lightly snoring as the dental surgical resident began intraoral injections. Respirations were recorded as 16 breaths/min. The patient tolerated intraoral injections well. After the completion of all intraoral injections, 25 mcgs of fentanyl and 10 mgs of decadron, slow push, were administered.

Tooth No. 1 was extracted non-surgically first, with no discernable arousal to the patient. Tooth No. 32 was surgically extracted, with light snoring noted in the precordial. After tooth No. 32 was sutured, the resident began extraction of tooth No. 16. The patient moved away from the stimulus due to discomfort, and heart rate increased from 82 to 110 bpm.

The area around tooth No. 16 was re-localized with 2% lidocaine with 1:100,000 epinephrine with an additional 10 mgs of propofol bolus administered concurrently, and the patient calmed. Surgical extraction of tooth No. 16 was uneventful, as was tooth No. 17. An additional 25 mcgs of fentanyl and 1 mg versed were given at the beginning of the extraction of tooth No. 17. Propofol infusion was discontinued after completion of the extraction of tooth No. 17, prior to suture placement. 

A total of 100 mcgs of fentanyl, 6 mgs versed, and 230 mgs of propofol was used.


Dental/OMS anesthesia records show up to 350 to 400 mgs infused with a patient still able to verbally arouse and maintain respirations in the 12 to 16 breaths per minute range. These exodontia cases are on average 45 to 90 minutes.

In comparison, records from non-cannabis consuming patients show propofol administration ranges from 100 to 180 mgs administered in the same 45- to 90-minute timeframe. In review of the cases this author has performed, that is a nearly 30% to 45% increase in propofol administration, with patients having difficulty achieving deep sedation and responding negatively to pressure and able to lucidly verbalize.

A literature search in both PubMed and Google Scholar for the key terms THC, cannabis, marijuana, sedation, and propofol (tradename Diprivan) failed to find any articles describing the physiologic causes for the need of increased propofol delivery to cannabis consumers.

This article is not a scientific study, but rather a case report to describe the unusual sedation occurrences seen when the patient is a chronic cannabis consumer. It is most beneficial to the hands-on anesthesia clinician seeking a logical explanation for physiological causes for increased propofol use.

For the purposes of this article, 30 records were reviewed from self-reported daily THC consumers, either for medical or recreational purposes. Although the cohort is small, it illustrates the intended purpose of this article, which was to discover trends in increased propofol administration in THC consumers.

History of Cannabis FDA Scheduling

Cannabis is a documented Schedule 1 drug according to the Food and Drug Administration (FDA) drug scheduling guidelines. Per this definition, it has no accepted medical use and a concurrent potential for high abuse.6,7

This contradiction between the dubious FDA definition and current, accepted medical methodologies deserves explanation for the clinician to appreciate the evolving cannabis philosophies and politics.

Prior to the 1930s, cannabis was widely used worldwide, for nearly 8,000 years, and a popular ingredient with many over-the-counter medications in the United States in the 19th and early 20th century.8,9 For most of the nation’s history, cannabis was legal and used in both recreational and medicinal capacities.

But in the 1930s, Commissioner Harry Anslinger of the Federal Bureau of Narcotics testified before Congress that “Marihuana [sic] is an addictive drug which produces in its consumers insanity, criminality, and death.”10 Despite Anslinger’s unfounded claims and the 1944 Laguardia Report scientifically disproving the cannabis/violence connection, enough public clamor was present that in 1937 Congress criminalized marijuana.11,12

This decision set precedent for mandatory minimum sentencing laws.13,14 The 1972 Shafer Commission appointed by President Nixon recommended the immediate cessation of all criminal penalties since “neither the marijuana consumer nor the drug itself can be said to constitute a danger to public safety.”13,14

However, 1970s political pressure to eradicate antiwar organizations was aided by these groups’ association with cannabis, so the Controlled Substances Act of 1970 classified cannabis as an FDA Schedule 1 drug, therefore allowing its continued criminalization.6,7,14

Fast forwarding several decades, cannabis research has now proven that THC is medically effective in treating chemotherapy and AIDS-related nausea and appetite stimulation. It also poses no significant increase risk for lung cancer in its organic form, reduces opioid overdoses, decreases post-traumatic stress disorder (PTSD) episodes, and decreases seizure activity.14-16 But the question is if it aids sedation. The myth that cannabis is a relaxant and that its use will “mellow” a person out is deceptive.

Cannabis Pharmacodynamics

The three existing cannabis species are Cannabis indica, Cannabis sativa, and Cannabis ruderalis. The two species most commonly grown for consumer production are Cannabis indica and sativa.9,17,18 The cannabis varieties will not be discussed in this article, as they are numerous and can be genetically crossed.

Cannabis affects the body both mentally and physically. Its effect occurs in three main phases: relaxation and euphoria, introspection and metacognition, and increased anxiety and hunger.16-20 These phases are sequential and dose dependent. The lengths of each phase and the profoundness of consumer effects depend on the THC dosage, plant species, and subsequent strain.1,15,18

First, the consumer expresses feelings of euphoria and relaxation. If THC dosing remains low, this phase is prolonged. The consumer’s blood pressure decreases, and heart rate will maintain or slightly increase by 20 beats to compensate for the reduction in blood pressure. The feelings of hunger normally associated with cannabis use will not increase.18, 21-25

THC at low to moderate dosing levels will decrease insulin levels in the bloodstream, leading to decreases in sugar metabolism.21,24 As blood levels of THC increase, the consumer will experience feelings of deep thought and increased sensation awareness.18,20,26,27 This altered conscious perception disrupts cognitive information integration and leads to the second phase, introspection and metacognition.18,19,28,29

In the second phase, introspection and metacognition, the consumer will express increased sensitivity to sensations, increased sexual desire, and alterations in the perception of their environment. Introspection occurs as the consumer evaluates their own intellectual and emotional “self,” while metacognition manifests as the consumer’s desire to comprehend stimuli outside of their standard methodology. In this phase, auditory and visual hallucinations can occur.16-19,27-29

In the third phase, increased anxiety and hunger, the highly lipid-soluble cannabinoid molecule binds with the body’s lipid membranes with the highest affinity for neuronal plasma membranes.16-19,30 When bound with THC, depolarized neurons exhibit a sluggish, impaired action potential, similar to persons with autism or schizophrenia.31-34 

Mental-health researchers theorize that genes associated with these two mental disorders corresponded with genes affected in THC treatments and that THC exposure impairs shared schizophrenia-neuronal pathways.33,34 Classified as spectrum disorders, autism and schizophrenia express “schizotypal traits” of cognitive-perceptual consciousness dysfunction, increased interactive anxiety, and disorganized behavior and speech.31-34 Impaired social and communication patterns seen in autism and schizophrenia are similar to the disrupted patterns of prolonged THC consumption.34

Cannabis Pharmacokinetics

A characteristic shared among the common intravenous sedatives propofol and fentanyl and marijuana is their capability to dissolve in the body’s fatty tissues. All three are highly lipid soluble and compete within the lipid-rich neuronal membranes.35,36

The body possesses a endocannabinoid system. Competition between lipid soluble sedatives during a one-time administration must compete with chronic administrations of THC. Where THC has the advantage over propofol is in its complexity to diffuse freely to other neurotransmitters, slowing its distribution and metabolism.37

The mechanism that makes propofol such a wonderful procedural sedative is its weakness when competing against THC, and that is its ability to rapidly redistribute into the plasma, well-perfused organs, and fast metabolism.38

When examining the pharmacokinetics of both THC and propofol, exposure to THC, especially daily exposure, results in higher neuronal lipid concentrations where THC is trapped within the neurotransmitters and propofol is rapidly cleared.37,38

THC binding and metabolism begins when cannabinoid receptors CB1 and CB2 are modulated. CB1 is predominantly located in the brain with few receptors in the periphery, and CB2 is predominately located in the immune cells of peripheral tissues with a lesser presence in the non-neuronal cells of the central nervous system (CNS).16,39,40

Triggering of CB2 initiates an anti-inflammatory response in the peripheral tissues, and it does not contribute to the failure of sedation in chronic cannabis users.41 However, modulation of CB1 activates the basal ganglia and limbic regions of the brain that regulate emotion, behavior, motivation, and memory.30,34,39-41

CB1 triggering, via THC attachment, decreases the inhibitory neurotransmitter, gamma-Aminobutryic acid (GABA), which is responsible for decreasing neuron excitability, and it disrupts GABA-mediated impulse transmission.9,16,42-44 CB1 increases the release of the catecholamines, particularly dopamine, which increases anxiety and heart rate, and potentiation of the body’s natural opioid receptors, which aid in endogenous pain management.9,39,45-50

Hejazi, Zhou, et al, discovered that as little as 300 nM of THC potentiates glycine-activated inhibitor currents.47 Glycine is an amino acid that functions as a CNS inhibitor as well as a co-agonist with glutamate.47,48

THC can bind directly to glycine receptors, decreasing receptor site availability to endogenous glycine.47 This, along with the ability for THC to bind directly to glycine, forms a THC-glycine complex that allows for potentiation of glycine receptors with less glycine needed, further allowing more free, unbound glycine in the body.47 The free unbound glycine then can lengthen CNS inhibition beyond what a provider has anticipated.

THC also increases extracellular glutamate and increases dopamine levels.45 Glycine and glutamate are both required for effective gating and excitation of the N-methyl-D-Aspartic acid (NMDA) receptor.49 Further disruption to internal neurotransmitter action occurs when THC increases levels of dopamine and glutamate, concurrently decreasing GABA pathways.

This disruption between neurotransmitters glycine, glutamate, and dopamine contribute to increases in NMDA receptor activity, while simultaneously decreasing GABA activity.44-49 NMDA is an excitatory neurotransmitter in the CNS that increases the body’s activity and agitation levels.49-51 THC-induced deviations in glycine and antagonism of GABA, coupled with the stimulated NMDA receptors, can cause hyperekplexia, which is an increased startle reflex response.53,54  

Propofol Pharmacokinetics

Propofol is a common sedative used in healthcare centers and dental offices in the United States. As noted earlier, anecdotal evidence shows the increased need for propofol volumes in patients who use cannabis, ranging from a 20% to a 45% increase.

Exploring the pharmacokinetics of propofol, the FDA classifies it as a general anesthetic. It is a sedative amnestic that has no true pain attenuation. It also is a profound respiratory depressant, vasodilator, and bronchodilator. It disrupts information integration as well.55,56

Furthermore, propofol increases GABA receptor activity, a chief inhibitory neurotransmitter, with binding action in the CNS to decrease muscle tone and increase amnestic effects.50,57 Propofol also has inhibitory action in sodium channel blockade, has suspected endocannabinoid activity at the CB1 and CB2 receptor sites, and reduces the release for systemic catechlamines.55,58 Through GABA activation and neuronal transmission, propofol induces and maintains either profound sedation or general anesthesia.55-57

Propofol Versus Cannabis in the Body

Empirically, sedation practitioners are reporting the need for increased levels of propofol when a patient is on sustained, daily use of cannabis. Clinically, patients with typical levels of propofol for a moderate or deep sedation are fully awake and talking lucidly. So what is going on? An exploration of the pharmacokinetics may offer a clue.

As stated above, propofol triggers the GABA receptor in the CNS to decrease consciousness, increase amnesia, and decrease muscle tone. THC potentiates the glycine pathways as explained above, causing neurotransmitter inhibition. THC-induced glutamate and dopamine simultaneously activate NMDA, and CB1 activation decreases GABA.45,49-51,58

In exploring this complex chemical relationship, propofol is attempting to activate GABA for inhibition, while cannabis is simultaneously causing glycine-receptor neuro-inhibition and NMDA systemic excitability. Propofol is attempting to inhibit catecholamines, while cannabis increases systemic catecholamines.

Both propofol and cannabis alter perception to affect short-term information assimilation and change the subject’s response to immediate events. However, propofol achieves this by inducing drowsiness, while cannabis achieves this by inducing a psychoactive state.11,29,56 Cannabis has known CB1 receptor activity, while propofol has suspected CB1 activity.41,50

After this lengthy look at the pharmacokinetics, the bottom line is that the beneficial effect of propofol is diminished due to cannabis’ ability to increase the body’s flight or fight hormones, particularly dopamine, and increase the body’s excitatory receptors, specifically NMDA.49-51,57,58 Constantly high levels of systemic THC easily overpower the sedative effect of the one-time exposure to propofol.  


With propofol being a short-acting, single-event administered dose, up against chronic THC usage and saturated body levels, cannabis effects will win out nearly every time. Thus, if sedation providers want to obtain the effects of propofol for their patients, they will have to increase their propofol dosing to overpower the THC molecule or change their approach to the sedation with an alternative drug regimen.

There is no evidence either empirically or scientifically that cannabis reduces the potential adverse effects of propofol overdose. The experienced sedation practitioner should understand that increasing propofol levels does increase the risk of an apneic event and increase the risk of hypotension with reflexive tachycardia.53

With the subsequent dosing of diphenhydramine, it has been noted for most chronic THC patients that while consciousness is not considerably decreased, clinically, patients settle considerably. Even though this article’s focus is not to introduce sedation techniques, it does note that the use of ketamine for chronic cannabis patients results in very satisfactory decreases in talking and agitation. This may be due to the fact that ketamine is an uncompetitive antagonist and needs an NMDA agonist, like THC, first to activate NMDA.59 Ketamine administration for cannabis patients may be explored in a future article.

Alternatively, the sedation practitioner can plan to avoid the use of the GABA or NMDA pathways. Sedative drugs such as muscle relaxants that antagonize serotonin receptors, alpha-2 adrenergic agonists, or antihistamines that rely on H1 receptor activity can be paired with increased local anesthetics, opioids, non-steroidal anti-inflammatory drugs (NSAIDs), or acetaminophen to achieve a level of surgical comfort for both the surgical team and the patient.

Dr. Flores attended dental school at the University of Texas Dental Branch in Houston. After graduation, he attended the University of Pittsburgh School of Dental Medicine, where he completed his specialty training in dental anesthesiology. Dr. Flores has received a dual-board certification in Dental Anesthesiology and was awarded Diplomate status with the American Dental Board of Anesthesiology and Fellow status with the American Dental Society of Anesthesiology. He obtained his MHA in 2018 and serves as the Department of Dental Medicine chief, clinic director, and director of dental anesthesiology for the University of New Mexico’s Ambulatory Surgical Center, Assistant Residency Director for AEGD residency, and chairman of the NM Anesthesia Commitee. He can be reached at


  1. Atakan, Z. (2012). Cannabis, a complex plant: different compounds and different effects on individuals. Therapeutic advances in psychopharmacology, 2(6), 241-254.
  2. MacCallum, C.A., & Russo, E.B. (2018). Practical considerations in medical cannabis administration and dosing. European journal of internal medicine, 49, 12-19.
  3. Bahorik, A.L., Leibowitz, A., Sterling, S.A., Travis, A., Weisner, C., & Satre, D.D. (2017). Patterns of marijuana use among psychiatry patients with depression and its impact on recovery. Journal of affective disorders, 213, 168-171.
  4. Phatak, U.P., Rojas-Velasquez, D., Porto, A., & Pashankar, D.S. (2017). Prevalence and patterns of marijuana use in young adults with inflammatory bowel disease.Journal of Pediatric Gastroenterology and Nutrition, 64(2), 261-264.
  5. Twardowski, M.A., Link, M.M., & Twardowski, N.M. (2019). Effects of Cannabis Use on Sedation Requirements for Endoscopic Procedures. The Journal of the American Osteopathic Association, 119(5), 307.Drug Scheduling. (n.d.). Retrieved July 22, 2019, from
  6. FDA (2016, April 12). FDA Regulation of Marijuana: Past Actions, Future Plans. Retrieved from
  7. Bachhuber M.A., Saloner B., Cunningham C.O., Barry C.L. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668–1673. doi:10.1001/jamainternmed.2014.4005
  8. Gray, Alice William et al. “Origins of Agriculture.” Encyclopædia Britannica. Encyclopædia Britannica, Inc., 29 Sep. 2015.
  9. Russo, E.B. (2013). Cannabis and cannabinoids: pharmacology, toxicology, and therapeutic potential. Routledge.
  10. Booth, M. (2015). Cannabis: a history. Macmillan.
  11. United States. Commission on Marihuana, & Drug Abuse. (1972). Marihuana: a Signal of Misunderstanding: The Technical Papers of the First Report of the National Commission on Marihuana and Drug Abuse. Appendix(Vol. 1). US Government Printing Office.
  12. Backstory Radio. “All Hopped Up: Drugs in America.” Virginia Foundation for the Humanities, 16 Aug. 2013.
  13. Bienenstock, D. (2018, November 14). The Most Impactful Cannabis Studies of All Time. Retrieved July 29, 2019, from
  14. Baum, Dan. “Legalize It All.” Harper’s Magazine. Harper’s Magazine Foundation, Apr. 2016.
  15. Bello, J. (2007). The benefits of marijuana: Physical, psychological and spiritual. Lifeservices Press.
  16. Pertwee, R.G. (2006). The pharmacology of cannabinoid receptors and their ligands: an overview. International journal of obesity, 30(S1), S13.
  17. Small, E., & Cronquist, A. (1976). A practical and natural taxonomy for Cannabis. Taxon, 405-435.
  18. Osborne, G.B., & Fogel, C. (2008). Understanding the motivations for recreational marijuana use among adult Canadians. Substance use & misuse43(3-4), 539-572.
  19. Ranganathan, M., & D’Souza, D.C. (2006). The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology188(4), 425-444.
  20. Kirkham, T.C. (2009). Cannabinoids and appetite: food craving and food pleasure. International Review of Psychiatry21(2), 163-171.
  21. Le Strat, Y., & Le Foll, B. (2011). Obesity and cannabis use: results from 2 representative national surveys. American journal of epidemiology174(8), 929-933.
  22. (2018, June 22). Marijuana. Retrieved July 22, 2019, from
  23. Vercauteren, K. (2013). ECON 330: Behavioral Economics Intertemporal Choice and Risk Preferences: Understanding Marijuana Use and Sexual Behavior June 9, 2013.
  24. Penner, E.A., Buettner, H., & Mittleman, M.A. (2013). The impact of marijuana use on glucose, insulin, and insulin resistance among US adults. The American journal of medicine126(7), 583-589.
  25. Haney, M., Malcolm, R.J., Babalonis, S., Nuzzo, P.A., Cooper, Z.D., Bedi, G., … & Walsh, S.L. (2016). Oral cannabidiol does not alter the subjective, reinforcing or cardiovascular effects of smoked cannabis. Neuropsychopharmacology, 41(8), 1974.
  26. White, C.M. (2019). A Review of Human Studies Assessing Cannabidiol’s (CBD) Therapeutic Actions and Potential. The Journal of Clinical Pharmacology.
  27. Johnson, B.A. (1990). Psychopharmacological effects of cannabis. British journal of hospital medicine, 43(2), 114-6.
  28. Marconi, A., Di Forti, M., Lewis, C.M., Murray, R.M., & Vassos, E. (2016). Meta-analysis of the association between the level of cannabis use and risk of psychosis. Schizophrenia bulletin42(5), 1262-1269.
  29. National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. National Academies Press.
  30. Mary Lynn Mathre, R.N. (Ed.). (2012). Cannabis in medical practice: a legal, historical and pharmacological overview of the therapeutic use of marijuana. McFarland.
  31. Hollister, L.E. (1986). Health aspects of cannabis. Pharmacological reviews38(1), 1-20.
  32. Guennewig, B., Bitar, M., Obiorah, I., Hanks, J., O’Brien, E.A., Kaczorowski, D.C., … & Barry, G. (2018). THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Translational psychiatry8(1), 89.
  33. Ford, T.C., & Crewther, D.P. (2014). Factor analysis demonstrates a common schizoidal phenotype within autistic and schizotypal tendency: implications for neuroscientific studies. Frontiers in psychiatry5, 117.
  34. King, B.H., & Lord, C. (2011). Is schizophrenia on the autism spectrum? Brain research1380, 34-41.
  35. Alexander, J.C., & Joshi, G.P. (2019, July). A review of the anesthetic implications of marijuana use. In Baylor University Medical Center Proceedings (Vol. 32, No. 3, pp. 364-371). Taylor & Francis.
  36. Khan, K.S., Hayes, I., & Buggy, D.J. (2014). Pharmacology of anaesthetic agents I: intravenous anaesthetic agents. Continuing Education in Anaesthesia, Critical Care & Pain, 14(3), 100-105.
  37. Zou S., Kumar U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences, 19(833): 1-23.
  38. Dinis-Oliveira, R.J. (2018). Metabolic profiles of propofol and fospropofol: clinical and forensic interpretative aspects. BioMed research international, 2018.
  39. Wilson, R.I., & Nicoll, R.A. (2002). Endocannabinoid signaling in the brain. Science296(5568), 678-682.
  40. Reitz, A.B., Choudhary, M.I., & Kordik, C.P. (Eds.). (2010). Frontiers in Medicinal chemistry(Vol. 1). Bentham science publishers.
  41. Joy, J.E., Watson, S.J., & Benson, J.A. (1999). Marijuana and medicine. Assessing the Science Base. Washington DC: National Academy.
  42. Oleson, E.B., & Cheer, J.F. (2012). A brain on cannabinoids: the role of dopamine release in reward seeking. Cold Spring Harbor perspectives in medicine, 2(8), a012229.
  43. Elphick, M.R., & Egertova, M. (2001). The neurobiology and evolution of cannabinoid signaling. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1407), 381-408.
  44. Watanabe, M., Maemura, K., Kanbara, K., Tamayama, T., & Hayasaki, H. (2002). GABA and GABA receptors in the central nervous system and other organs. In International review of cytology (Vol. 213, pp. 1-47). Academic Press.
  45. Pistis, M., Ferraro, L., Pira, L., Flore, G., Tanganelli, S., Gessa, G.L., & Devoto, P. (2002). Δ9-Tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study. Brain research, 948(1-2), 155-158.
  46. Kathmann, M., Flau, K., Redmer, A., Tränkle, C., & Schlicker, E. (2006). Cannabidiol is an allosteric modulator at mu-and delta-opioid receptors. Naunyn-Schmiedeberg’s archives of pharmacology, 372(5), 354-361.
  47. Abadinsky, H. (2004). Drugs: An introduction. Wadsworth Publishing Company. (5th ed.). pp. 62–77, 160–166.
  48. Hejazi, N., Zhou, C., Oz, M., Sun, H., Ye, J.H., & Zhang, L. (2006). Δ9-Tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors. Molecular pharmacology69(3), 991-997.
  49. Liu, Y., & Zhang, J. (2000). Recent development in NMDA receptors. Chinese medical journal, 113(10), 948-956.
  50. N-Methyl-D-aspartic acid. (n.d.). Retrieved July 31, 2019, from
  51. Paoletti, P., & Neyton, J. (2007). NMDA receptor subunits: function and pharmacology. Current opinion in pharmacology, 7(1), 39-47.
  52. Mistretta, O.C. (2016). The Effects of Δ9-tetrahydrocannabinol (THC) on development and hyperekplexia in embryonic zebrafish model.
  53. Xiong, W., Chen, S. R., He, L., Cheng, K., Zhao, Y. L., Chen, H., … & Wu, L.G. (2014). Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. Nature neuroscience, 17(2), 232.
  54. Xiong, W., Cheng, K., Cui, T., Godlewski, G., Rice, K. C., Xu, Y., & Zhang, L. (2011). Cannabinoid potentiation of glycine receptors contributes to cannabis-induced analgesia. Nature Chemical Biology7(5), 296.
  55. Trapani, G.M., Altomare, C., Sanna, E., Biggio, G., & Liso, G. (2000). Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Current medicinal chemistry, 7(2), 249-271.
  56. Thompson, S.A., & Wafford, K. (2001). Mechanism of action of general anaesthetics—new information from molecular pharmacology. Current opinion in pharmacology, 1(1), 78-83.
  57. Propofol Monograph for Professionals. (n.d.). Retrieved July 30, 2019, from
  58. Dingledine, R., Borges, K., Bowie, D., & Traynelis, S.F. (1999). The glutamate receptor ion channels. Pharmacological reviews51(1), 7-62.
  59. Roth, B.L., Gibbons, S., Arunotayanun, W., Huang, X.P., Setola, V., Treble, R., & Iversen, L. (2013). The ketamine analogue methoxetamine and 3-and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One, 8(3), e59334.

Related Articles

The Importance of Vital Signs

Seven Protective Reflexes Every Dentist Should Know

What Is a Dentist Anesthesiologist?