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Increased Blood Pressure Following Abrupt Cessation of Daily Cannabis Use

Abstract

Objective

Cannabis is the most widely used illicit drug. Acute cannabis administration increases blood pressure and heart rate and tolerance develops to these effects with heavy use. A valid and reliable withdrawal syndrome occurs in most daily users, but few studies have assessed the cardiovascular effects of withdrawal. The objective of this report is to describe unexpected changes in cardiovascular function during brief periods of supervised cannabis use and abstinence in daily cannabis users.

Methods

A within-subjects ABAC crossover study in which inpatient volunteers smoked cannabis ad-libitum (A), and abstained from cannabis (B/C). Vital signs were obtained three times daily during eleven inpatient days for thirteen daily cannabis users (11 Male, 8 African American).

Results

Blood pressure increased significantly during periods of cannabis abstinence compared with periods of cannabis use. The magnitude of increase was substantial in a subset (N=6) of participants, with mean increases of up to 22.8mmHg systolic and 12.3mmHg diastolic blood pressure observed. Heart rate also increased during abstinence when measures collected during periods of acute intoxication were excluded, but the magnitude of effect was not clinically significant.

Conclusions

Abrupt cessation of heavy cannabis use may cause clinically significant increases in blood pressure in a subset of users. Blood pressure should be monitored among those attempting to reduce or quit frequent cannabis use, particularly those with preexisting hypertension. The time course of this effect is currently unknown and requires further study.

Background

Cannabis (marijuana, hashish) is the most widely used illicit drug in the world with an estimated 160 million current users (UNODC, 2007). In the past decade, treatment admissions for cannabis use disorders have increased significantly, and the number of people who meet criteria for dependence on cannabis now exceeds the number who meet dependence criteria for any other illicit drug (UNODC, 2007; AIHW, 2008; EMCDDA, 2008; SAMHSA, 2008). Despite such widespread use and abuse, relatively little is known about the cardiovascular effects and possible associated health risks associated with chronic cannabis use.

Acute cannabis administration has been shown to increase resting heart rate and blood pressure, and induce orthostatic hypotension (Jones, 2002). Increased heart rate following acute cannabis exposure has been shown to be dose-related (Heishman et al., 1989). Peak effects on heart rate appear to occur 10 to 15 minutes after smoking and result in an increase of 20 to 30 beats per minute, but mean increases as high as 43.5 beats per minute have been reported (Chait and Zacny, 1992; Galanter et al., 1972; Heishman et al., 1989; Ilan et al., 2005). There are few studies in which the effects of smoked cannabis administration on blood pressure are reported. Supine blood pressure has been shown to increase following cannabis exposure (Mathew et al., 1993), but blood pressure has also been shown to drop when participants move from a supine to standing position (Renault et al., 1974). Insufficient published data are available to confidently report on the time course or typical magnitude of these effects, and it appears that orthostatic hypotension is reliably observed whereas an increase in supine blood pressure is not. Epidemiological studies and case reports have linked acute cannabis intoxication to myocardial infarction, angina, arrhythmias, transient ischemic attacks, and stroke (Karch, 2006). However, associations between cannabis use and these cardiovascular events are not always consistent, case reports of these types of occurrences are rare, and controlled studies are generally lacking.

Tolerance to the acute cardiovascular effects of cannabis develops rapidly with repeated exposure. In laboratory studies, the acute cardiovascular effects of delta-9-tetrahydrocannabinol (THC; the primary psychoactive component of cannabis) are attenuated with repeated administration, and have even been shown to result in a reduction of heart rate and blood pressure relative to baseline levels (Benowitz and Jones, 1975; Benowitz and Jones, 1981). However, Jones (Jones, 2002) recently pointed out that understanding of the cardiovascular effects of chronic cannabis use is limited by the fact that most human research has been of short duration, used relatively low doses of smoked cannabis or oral THC, and has largely excluded participants who are female, older, or exhibit symptoms of cardiovascular disease.

Because tolerance develops to the acute cardiovascular effects of cannabis with repeated use, it is plausible that a rebound increase in heart rate and blood pressure would be observed following abrupt cessation of heavy use. Recent research has demonstrated that a reliable, valid, and pharmacologically specific withdrawal syndrome occurs in a majority of heavy (daily) cannabis users when they abruptly stop use (Budney et al., 2004; Haney, 2005; Budney and Hughes, 2006), but few published studies of cannabis withdrawal effects have included cardiovascular measures. In a recent outpatient study of cannabis withdrawal, heart rate was higher during abstinence compared with periods of cannabis use (Vandrey et al., 2008). In that study a trend towards increased systolic blood pressure during abstinence was also observed, but was not statistically significant. However, no effect of withdrawal was found on cardiovascular function (HR or BP) in two similar outpatient studies from the same laboratory (Budney et al., 2001; Budney et al., 2003).

This paper describes cardiovascular effects observed during a study of hypnotic medication effects in heavy cannabis users. High blood pressure readings (SBP>160mmHg, DBP >90mmHg) were observed for several study participants during periods of cannabis abstinence, and most of these subjects had no prior evidence of hypertension on study admission or during study periods when cannabis use was allowed. Based on these observations a specific exclusion criterion was adopted prior to study completion to exclude those who exhibited any evidence of hypertension during the study intake process. Here we report on findings from study participants who completed participation prior to the implementation of the hypertension exclusion criterion.

Methods

The study procedures were reviewed and approved by the John Hopkins Medicine Institutional Review Board and conducted in accordance with the ethical standards of the Helsinki Declaration. A within-subject crossover design was used in which participants completed two 5-day inpatient study phases consisting of an initial 2-day period during which participants were allowed to use cannabis ad libitum between 12:00 and 21:00, followed immediately by a 3-day period of forced cannabis abstinence. During one cannabis abstinence period, participants were administered extended-release zolpidem each night at bedtime, and during the other abstinence period placebo was administered. The order in which participants received zolpidem or placebo was counterbalanced across participants. The inpatient study phases were separated by an 8-day outpatient washout period, during which daily cannabis use was reestablished in the participants’ home environment.

Daily cannabis users were recruited to participate in the study via newspaper advertisements. Participants were between 18–55 years of age; used cannabis at least 25 days per month for at least 1 year with no indication that they were seeking treatment for cannabis or using cannabis for medical purposes; had no current Axis I psychiatric disorders other than cannabis or nicotine dependence; were not currently taking psychoactive medication; were not pregnant or breastfeeding; and provided a urine specimen that was positive for THC and negative for other drugs of abuse at study intake. Informed consent was obtained for all participants.

Fourteen participants were enrolled and 13 completed the study (11 male, 2 female). Those who completed the study were mostly African American (N=8), had a mean (SD) age of 31 (9) years, had been using cannabis at least once per week for 16 (9) years, and used cannabis an average of 5 (3) times per day during the 3 months prior to admission in the study. Alcohol and other drug use were infrequent among participants, but all smoked tobacco cigarettes (6 (5) cigarettes/day) daily. One male African American participant (017) was taking lisinopril (20mg/day) and hydrochlorothiazide (12.5mg/day) for hypertension on admission to the study. This medication regimen had been stable for 12 months and was continued uninterrupted during study participation except for one day when lisinopril was increased to 40mg following 2 days of sustained elevated blood pressure during his second cannabis abstinence period. No other study participants reported current or past cardiovascular disease.

Resting heart rate and supine blood pressure were measured at 10:00, 16:00, and 21:30 each day using an automated monitor (Criticare Systems Inc., Waukesha, WI).

A preliminary statistical test was conducted using a one-way analysis of variance (ANOVA) to determine if there was a main effect of drug condition (zolpidem versus placebo) on blood pressure and heart rate during the two cannabis abstinence periods. As expected, zolpidem did not affect daytime cardiovascular function compared with placebo. Because no effect of zolpidem was observed, data collected during the two abstinence periods were collapsed in subsequent analyses.

Blood pressure and heart rate assessments were then analyzed using a repeated measures regression model in which cannabis use condition (ad libitum use versus abstinence) and replication (first study phase versus second study phase) were entered as factors. This model was selected because the unbalanced number of assessments between the cannabis use and abstinence periods precluded use of parametric analyses without either collapsing data into means by cannabis use condition (which would have reduced natural variability) or excluding one day of data during the abstinence condition. The effects of cannabis on blood pressure and heart rate were assessed using Tukey’s post-hoc tests by comparing measures obtained at 10:00 (prior to ad libitum cannabis use) with measures obtained at 16:00 and 21:30 (after initiation of ad libitum cannabis use) on study days in which cannabis smoking was allowed. Data analysis was conducted using SAS statistical software Version 9.1 (Cary, NC).

Results

Significant main effects of cannabis use condition were observed for systolic blood pressure (F = 47.05, p Figure 1 shows mean cardiovascular measures collapsed across participants and study phases. Figure 2 shows mean blood pressure measures of 6 participants for which the most pronounced abstinence effects on cardiovascular parameters were observed. These participants, roughly half of the study sample, each showed a mean blood pressure increase that was greater than the mean increase for the entire study sample during abstinence (10mmHg SBP and 7mmHg DBP). In this sub-group of participants, systolic blood pressure increased from a mean (SEM) of 130.9 (2.1) mmHg during cannabis use to a mean of 146.6 (3.1) mmHg during abstinence, and diastolic blood pressure increased from a mean of 78.1 (2.4) mmHg during cannabis use to a mean of 87.0 (2.9) mmHg during abstinence.

Mean systolic blood pressure (Panel A), diastolic blood pressure (Panel B), and 10:00am heart rate assessments collapsed across participants (N=13). The * indicates a significant difference (p 140 mmHg diastolic blood pressure of > 90 mmHg, although lower parameters (≤130/80) are recommended among patients with other cardiovascular risk factors such as diabetes (Chobanian et al., 2003). In the present study, none of the heavy cannabis users had average blood pressure in the hypertensive range during periods of cannabis use, but 4 of 13 (31%) and 2 of 13 (15%) of participants had average blood pressure assessments in the hypertensive range for SBP and DBP respectively during abstinence. Research also indicates that every increase of 20 mmHg systolic and 10 mmHg diastolic blood pressure above 115/75 mmHg results in a doubling of relative risk for cardiovascular disease related mortality (Chobanian et al., 2003). One participant in this study had a mean increase of 22.8 mmHg systolic and 12.3 mmHg diastolic blood pressure, and the half of the study sample showing the greatest effect had mean increases of 15.7 mmHg systolic and 8.9 mmHg diastolic blood pressure. This indicates that the magnitude of the increase in blood pressure observed in this study is clinically meaningful.

There were no clear demographic or cannabis use characteristics that predicted the magnitude of effect observed for individual study participants. While most study participants were male, one of the two female participants was among the subgroup that showed the greatest increase in blood pressure suggesting that this effect is not gender specific. However, with only two female participants we cannot establish whether there are gender differences in the magnitude of cardiovascular response to cannabis cessation. It is also important to note that the participants in this study were older and more likely to be African American compared with prior studies of cannabis withdrawal that included cardiovascular measures. Both age and African American heritage are established risk factors for hypertension (Kaplan, 1994). Also, though the majority of cannabis users are adolescents and young adults, approximately one-third of current users and 23–35% of treatment admissions for cannabis use disorders are age 30 or older (AIHW, 2008; SAMHSA, 2007, 2009). Thus, the current study is representative of a large sub-population of cannabis users, but one that has been generally underrepresented in prior studies.

Due to the short duration of abstinence in this study and the lack of pre-cannabis use cardiovascular measures, it is uncertain whether these effects are a product of cannabis withdrawal (i.e., a time limited increase) or if these effects represent a rebound or offset effect of cannabis-induced decrease in blood pressure and heart rate (i.e., a time unlimited increase). If these cardiovascular changes reflect a withdrawal effect, the cause may be a direct pharmacological withdrawal effect or secondary effects of other symptoms of cannabis withdrawal (e.g. anxiety). On the other hand, a rebound or offset effect would more clearly indicate a direct effect of the endocannabinoid system, and would have significant clinical implications. First, reduction or cessation of frequent cannabis use would be cause for evaluating and likely modifying ongoing treatment for cardiovascular disease among patients. Second, it would suggest the need for careful observation of cardiovascular effects (beneficial or harmful) in the development of medications that modulate the endocannabinoid system.

There are limitations of this study with regard to assessing the risk of an acute cardiovascular event occurring in cannabis users during a quit attempt. First, cardiovascular risk is limited to the duration of the effect, and it is uncertain whether the abstinence-induced effects observed persist for longer than 3 days. Most cannabis withdrawal effects last 1–2 weeks, though sleep-related symptoms have been shown to persist longer (Budney et al., 2003). Greater cardiovascular risk would be expected if the increase in blood pressure resulted from a rebound or drug offset effect, which would persist indefinitely. That said, most participants in this study (69%) did not exhibit cardiovascular effects large enough to meet accepted criteria for a diagnosis of hypertension. Thus, if there is a risk for an acute cardiovascular event as a result of increased blood pressure, it is likely limited to a minority of users, and, even then, may not present a true risk in the absence of other cardiovascular risk factors.

Accounting for all assessment points, there was no effect of cannabis abstinence on heart rate. A statistically significant effect of cannabis abstinence was observed when analysis was limited to assessments conducted in the morning, which eliminated time points that could have been affected by cannabis intoxication during the ad-libitum use periods. However, the increase observed in that analysis (increase of 5 bpm to mean of 81 bpm) does not indicate that this effect is likely to result in clinically relevant cardiovascular risk.

Conclusion

Cannabis withdrawal in this study resulted in a significant increase in blood pressure that was of sufficient clinical magnitude to suggest the need for recognition and further consideration with regards to research eligibility. This effect was reliably observed across 2 different abstinence periods. Mean blood pressure was qualitatively higher for all 13 participants during cannabis abstinence periods compared with ad libitum cannabis use periods, and the increase during abstinence resulted in mean blood pressure in the range of Stage 1 hypertension for 4 participants (31%). These were unexpected findings observed in a research study designed to investigate the effects of cannabis use and abstinence on sleep, and the limitations of the study design preclude understanding the mechanism or duration of this effect. Additional research is required to examine the time course and generality of these results. Studies with larger and more diverse samples (e.g., more females; those with risk factors for cardiovascular disease) may also help clarify whether specific risk factors or genotypes are associated with abstinence-induced hypertension in cannabis users. If additional research confirms these results, independent of the underlying cause and time course of the effect, heavy cannabis users who abruptly abstain should receive cardiovascular monitoring and treatment if indicated by established medical guidelines.

Acknowledgments

This publication was made possible by Grants R21-DA025794 and DA023186 from the National Institute on Drug Abuse (NIDA) and Grant UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The authors thank the research and medical staff of the Johns Hopkins Behavioral Pharmacology Research Unit and Clinical Research Unit for their valuable contributions to this work. The authors have no conflicts of interest to report in relation to this research. This study is registered at ClinicalTrials.gov ( <"type":"clinical-trial","attrs":<"text":"NCT00893269","term_id":"NCT00893269">> NCT00893269).

Research Support: Grants DA025794 (Vandrey) and DA023186 (Strain) from the National Institute on Drug Abuse (NIDA), and Grant UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research

Increased Blood Pressure Following Abrupt Cessation of Daily Cannabis Use Abstract Objective Cannabis is the most widely used illicit drug. Acute cannabis administration increases blood

How Does Marijuana Affect Blood Pressure? Here’s What the Science Says

The relationship between marijuana and high blood pressure is so complex that even the experts cannot agree on whether cannabis is safe for people with hypertension.

Some say that cannabis use increases the risk of cardiac arrest in people who already suffer from high blood pressure, while others state that more studies are needed to prove such claims.

And, according to seasoned weed vets and observational studies, cannabis initially causes a slight rise in blood pressure and then lowers it.

Most of the studies I found while writing this article also have opposing conclusions.

To find out the truth behind many claims regarding this topic, I decided to go through every important study dealing with the effects of weed on blood pressure and then present my findings in this guide.

Also, I’ll be looking into experiences of real users, which I believe are of the utmost importance in cases like this one.

What is high blood pressure (hypertension)?

Before we can dive into the effects of marijuana on blood pressure we first need to understand the difference between normal and high blood pressure.

As your heart beats, it pumps blood through your arteries. Blood pressure is determined by measuring the force of the blood pressing against the artery walls. The force of blood in the arteries when your heart pumps is measured as systolic pressure. The force measured at the moment of rest between heartbeats is diastolic pressure.

For most healthy adults, normal blood pressure is less than 120 millimeters systolic and less than 80 millimeters diastolic.

High blood pressure means the heart has to work harder to pump blood which causes strain and weakening. It also causes the walls of the arteries to get damaged over time.

High blood pressure is a cardiovascular condition which occurs when the blood pressure in arteries is constantly elevated.

Hypertension affects about a third of adult Americans and around 17.7% of Canadians. The condition usually does not cause any symptoms and it is often only discovered during a medical checkup. Hypertension is not something that should be ignored. It can cause serious health problems if left untreated.

As with many other conditions, there are certain risk factors that can influence the development of the disease; genetics, smoking tobacco, drinking alcohol, obesity, poor diet and stress all play a role.

What does science have to say about cannabis and hypertension?

There are currently only a few studies on the influence of cannabis on blood pressure and the studies can be contradictory.

But here is what I found.

THC and hypertension

A study published in August 2017, titled “Effect of marijuana use on cardiovascular and cerebrovascular mortality” (1) is one of the most quoted studies on marijuana and high blood pressure.

This paper concluded that regular cannabis users are more likely to die from hypertension and that the length of time that marijuana was used increases the risk.

But there is one huge problem with it:

It’s made of participants who used cannabis “at least once in their life”, so we basically have no idea whether the subjects continued to smoke every day or they just smoked once in high school. This leaves a lot of room for misinterpretation.

There are a few studies that suggest that occasional users may experience a mild or moderate increase in heart rate, with a slight increase in blood pressure 10-15 minutes after consuming cannabis. (2)

These studies claim that, after the initial increase, our blood pressure drops, leaving us sleepy and groggy (sounds familiar, right?).

Some cannabis consumers can also develop tolerance to uncomfortable side effects of pot just a few days or weeks after using it.

When it comes to more severe consequences of high blood pressure related to cannabis use, we can only rely on CARDIA’s report, which investigated more than 3,500 Americans over the course of 15 years. (3)

The results might sound surprising at first:

No long-term connection was found between marijuana and cardiovascular diseases, such as heart attack and stroke.

However, the study also pointed out this:

“Although marijuana use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use.”

The risk of having a heart attack is increased five times during the first hour after smoking cannabis but then drops 1.7 times during the next hour. The risk returns to normal after two hours.

At this point, it’s important to note that many other everyday activities bring with them a much higher risk of heart attack, such as sex.

There have been a few reported cases of people having a heart attack after smoking weed. As you may assume, it’s impossible to conclude if weed and its influence on blood pressure was the main culprit in these cases.

Can CBD lower blood pressure?

The problem with the studies I found is that most of them are focused only on one cannabinoid in the cannabis plant — the psychoactive, tetrahydrocannabinol (THC).

Other than THC, cannabis contains more than 100 other cannabinoids and over 200 different terpenes.

Today, we have hundreds of different strains on the market, each with a different ratio of THC to CBD and each with different medical effects.

THC has been shown to make some people anxious, sometimes even paranoid (but these are usually just short-term effects, which go away as soon as the high wears off).

Elevated heart rate always goes hand in hand with anxiety, therefore it’s almost expected for some users to get an increase in blood pressure.

Exclusive bonus: Download a free dosage guide that will show you the exact step-by-step process Dr. Dustin Sulak used to successfully treat more than 18,000 patients with cannabis.

On the other hand, the second most abundant cannabinoid, the one that’s been stealing the spotlight lately, seems to have a completely opposite effect on blood pressure than THC.

I’m talking, of course, about cannabidiol, or better known as CBD — famous for reducing all types of anxiety and inflammation.

According to a small study published in JCI Insight, a single dose of CBD lowers systolic blood pressure. (4) Researchers found that CBD relaxes smooth muscle cells in the arteries, widens the blood vessels, thus providing a smoother blood flow and a lower blood pressure.

CBD and Blood Pressure: Can It Reduce High BP?

Strains for people who suffer from high blood pressure

Smoking is one of the main causes of high blood pressure.

If you are suffering from hypertension you should avoid smoking altogether, as it will most likely cause your blood pressure to increase further.

Smoking is not the only cannabis consumption method. Vaping and edibles (including oils) can be healthier alternatives to burning up a flower.

Arizer Extreme Q: Royalty Among Desktop Vaporizers

While I was doing research for this article, I glanced over some comments and threads on Reddit, and I found differing user opinions on the cannabis-hypertension relationship.

Some patients who used marijuana frequently got their blood pressure back into the normal range only after quitting weed completely.

Some patients smoke regularly and they claim weed helps keep their BP in check.

So, if you like weed and have been diagnosed with hypertension, my advice would be to:

● Consult your doctor
● Avoid smoking and instead, use one of the healthier ways of consuming weed
● Try exploring cannabis strains that are high in CBD
● Take smaller doses and don’t overdo it (baby steps are the best)

Start with the 5 strains I’ve listed below, little by little, and monitor your blood pressure after using pot.

If your blood pressure rises after using weed, quit smoking altogether.

You can live without smoking cannabis and your health and well-being should be your number-one priority at all times.

Purple Wreck

One of the most popular strains in the medical world, this thoroughbred indica is recommended for a variety of conditions.

Purple Wreck will give you full body relaxation while eliminating stress at the same time. This strain won’t make you sleepy as most indicas but it’s best used at night, as you close off your day.

Blue Dream

Also a very popular medical strain, Blue Dream provides calming relaxation and tension relief.

Northern Lights

Although this strain has a very high THC content, hypertension patients have reported good experiences with it. Northern Lights will help all your muscles relax.

Super Sour Diesel

Super Sour Diesel is a very potent strain, so take it easy with this one, as you would with any other strain rich in THC. Provided you get the dosage right, it will help you leave behind any stress, which is also one of the main causes of hypertension.

Green Crack

Formerly known as “Cush”, Green Crack got its new name from Snoop Dogg — after he tried this potent sativa, he joyously renamed it because of the energetic kick it brings.

Because of its sativa dominance, Green Crack is much better suited for daytime use, and with its moderate-to-high THC levels (between 15% and 20%) it is beneficial for a wide array of medical issues including chronic pain, arthritis, and depression. Even though the ominous name may suggest otherwise, do not fret, this is 100% quality cannabis flower.

Find out everything about the studies explaining the effects of THC and CBD on hypertension and discover the best strains for keeping the blood pressure low.