BHSynergy

Research: Effects of Cannabinoids on Female Sexual Function

December 6, 2019

Effects of Cannabinoids on Female Sexual Function

Becky Lynn, MD,1 Amy Gee, MD,1 Luna Zhang, BS,1 and James G. Pfaus, PhD2

ABSTRACT

Introduction: With the legalization of both medical and recreational marijuana in some countries and a few US states, its use has become more widely prevalent. Both exogenous cannabinoids such as tetrahydrocannabinol (THC) and endogenous cannabinoids (endocannabinoids) have been shown to affect female gonadotropin pathways and female sexuality. Yet, our understanding of the mechanisms and effects on female sexual function is limited.

Aim: To review the literature regarding the effects of both endogenous and exogenous cannabinoids on female sexual function in both animals and humans.

Methods: We performed a PubMed search for English-language articles in peer-reviewed journals between 1970 and 2019. We used the following search terms: “cannabinoids,” “endocannabinoids,” “marijuana,” “cannabis,” and “female sexual function” or “sexual function.” The main outcomes of the papers were reviewed.

Main Outcome Measure: The main outcome measure was sexual function in females.

Results: A total of 12 human studies and 8 animal studies that evaluated the relationship between cannabinoids and female sexual function were included. Study types in animals were blinded, prospective, placebo-controlled trials. Human studies were based primarily on questionnaire data. The data indicate dose-dependent effects on female sexual desire and receptivity, such that low doses generally facilitate or have no effect but high doses inhibit.

Conclusions: More research is needed to develop a better understanding of the effects of cannabinoids on female sexual function. There does appear to be an effect on both animals and humans, but whether the effect is positive or negative along dose and species lines requires more study. With the legalization of marijuana occurring in more countries and more US states, there needs to be more well-controlled studies evaluating the effects. Lynn B, Gee A, Zhang L, et al. Effects of Cannabinoids on Female Sexual Function. J Sex Med 2019; XX:XXXeXXX.

Copyright   2019, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Key Words: Endocannabinoids; Cannabis; Marijuana; Female Sexual Function; THC; Endocannabinoid System

INTRODUCTION

Marijuana use has become more widely prevalent over the last decade. Its use has been decriminalized in México and has been accepted into law for both medical and recreational purposes in

Received May 9, 2019. Accepted July 22, 2019.

1Department of Obstetrics, Gynecology and Women’s Health, Division of General Obstetrics and Gynecology, Saint Louis University School of Medicine, St. Louis, MO, USA;

2Centro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, México

Copyright ª 2019, The Authors. Published by Elsevier Inc. on behalf of

the International Society for Sexual Medicine. This is an open access

article  under  the  CC  BY-NC-ND  license  (http://creativecommons.org/

licenses/by-nc-nd/4.0/).

Canada and for use by the general population in several US states. As of the publication of this paper, 33 states and the District of Columbia had legalized marijuana for medical use, and 10 of those states legalized marijuana for recreational use.1 Good-quality research has long been lacking on the effects of marijuana on sexual function due to the illegality of the drug. The effects of marijuana on physiological mechanisms and be-haviors that drive sexual function have been studied primarily in rodents, and human research has had to depend on retrospective questionnaires. This paper aims to review the published data assessing the effects of cannabinoids on female sexual function.

METHODS

A literature review was performed in PubMed for publications in English with the keywords “marijuana,” “cannabis,”

“endocannabinoids,” and “sexual function” or “female sexual function.” We found 190 articles with these search qualifications, and the abstracts of these 190 articles were reviewed. Articles were included if they featured a study or survey that measured the impact of marijuana usage on female sexual function in an-imals and/or humans. Citations in these articles were then also reviewed for relevance. Given the scarcity of research done on humans relating to marijuana usage and sexual function, any relevant article was selected. No particular type of study was excluded or sought out. Twelve articles were identified relating to human research and were reviewed; of these 12 articles, 11 were retrospective surveys, and 1 was a prospective cohort study. Eight prospective, randomized, blinded animal studies were included. No particular animal species was included or excluded, but the animal studies relevant to this review were largely done on rats. Our main outcome measure was sexual function in females.

Endocannabinoid System

The first biologically active component of cannabis was identified in the 1960s as D9- tetrahydrocannabinol (THC), a

potent drug classified as a sedative-hypnotic. This was followed by the discovery of 2 cannabinoid receptors, CB1 and CB2, in the early 1990s.2 Both are G-protein-coupled receptors and serve as the primary site of action for THC. Together, they are involved in a major neuromodulatory system known as the endocannabinoid system (ECS). The primary goal of the ECS is to promote homeostasis.3 The main components of the ECS are the receptors CB1 and CB2; their endogenous ligands, ananda-mide (AEA) and 2-arachidonoylglycerol; and the enzymes that modulate their breakdown (fatty acid amide hydrolase and monoacylglycerol lipase). They are synthesized by fatty-acid metabolism and located in neurons, where they are released on demand by simple diffusion (Figure 1).4

The ECS is widespread throughout the body, including the central and peripheral nervous systems. The cannabinoid re-ceptors differ in their location of distribution. CB1 receptors are found throughout the central nervous system and some periph-eral tissues. CB2 receptors, on the other hand, are primarily found in peripheral tissues and immune cells. Centrally, these receptors are more densely expressed in the neurons of

Figure 1. The endocannabinoid system: its functions, distribution, and components. Figure 1 is available in color online.

Effects of Cannabinoids on Female Sexual Function 3

hypothalamus, hippocampus, amygdala, cerebral cortex, parts of the basal ganglia, and cerebellum. Peripherally, cannabinoid re-ceptors are found in organs responsible for producing sex hor-mones, such as the adrenals, which provide a source of androgens, and the ovaries, which provide a source of estrogen, progesterone, and androgens.5 Other biologically active canna-binoids (reviewed in Cohen et al6) have been discovered in marijuana, including cannabidiol, which is beginning to show promise in blocking pain and inflammation and for use as an antiepileptic medication; cannabigerol, which can treat the intraocular pressure associated with glaucoma; cannabichromene, which blocks pain and inflammation and shows encouraging anticancer effects; and tetrahydrocannabivarin, which acts as an effective appetite suppressant, reduces anxiety without altering mood, and shows efficacy in maintaining blood sugar levels and reducing insulin resistance. However, in addition to their inter-action with CB1 and CB2 receptors, these molecules modulate the binding affinity of other neurotransmitter receptors (eg, dopamine, serotonin). Importantly, the effects of these molecules have not yet been tested on sexual behavior.

ECS and the Hypothalamic Pituitary Axis

Studies have shown that a relationship exists between the ECS and gonadal hormones. The ECS has been implicated in certain physiologic functions and behaviors that are known to be regu-lated by gonadal hormones. Many of the receptors and metabolic enzymes of the ECS are located extensively in the structures involved in the hypothalamic-pituitary-gonadal axis. In animal models, studies show that THC suppresses gonadotropin release through the blockade of gonadotropin-releasing hormone from the hypothalamus.4 This in turn causes decreased luteinizing hormone and follicle-stimulating hormone release from the anterior pituitary, resulting in decreased estrogen release from the ovaries and decreased progesterone release from the corpus luteum.4 Thus, overall, THC blunts the activation of hormones that affect female sexual function.

Cannabinoids and the Neurotransmitters That Affect Sexual Function

CB1 is a presynaptic receptor that results in inhibition of neurotransmitter release when activated.7 CB1 receptors are located in the axon terminals of GABAergic, dopaminergic, adrenergic, glumatergic, and cholinergic neurons. Haring et al8 also found evidence of CB1 receptors in a subset of seroto-nergic neurons. Of importance, dopamine and serotonin play key roles in sexual functioning.9 Dopamine and norepinephrine play a role in excitatory processes of sexual function, such as desire and arousal, and serotonin plays a role in inhibitory pro-cesses, such as loss of desire. These neurotransmitters interact with testosterone, estrogen, melanocortins, progesterone, pro-lactin, and oxytocin to modulate the female sexual response.10

In the early 1970s, interest grew in studying the effects of marijuana on sexual function. It was known that marijuana had

effects on reproductive function. Marijuana was found to lower testosterone, decrease the weight of the testes, and affect sper-matogenesis in male rats.11 In female rats, marijuana was shown to decrease the luteinizing hormone surge and inhibit ovulation.12e14 It was therefore postulated that, due to its in-fluence on reproductive hormones, marijuana and other endo-cannabinoids might diminish sexual function. At that time, however, work on the effects of marijuana on sexual behaviors was limited; therefore, studies were done with animals, primarily rodents, to further elucidate the link between cannabinoids, including marijuana and sexual function.

Preclinical Studies of the Effects of Cannabinoids on Sexual Function

In 1978, Gordon et al11 evaluated the effects of THC on female lordosis, a posture assumed by some female mammals during mating, in which the back is arched downward. In rats, lordosis is a measure of female sexual receptivity. One goal of the study by Gordon et al was to determine if THC acted like es-trogen or progesterone. When these hormones were absent, these researchers found there was no effect on lordosis; however, when these hormones were present, THC enhanced lordosis, although at very high doses it did not.11

In 1981, Turley and Floody15 found that THC stimulated lordosis (receptivity) and sexual solicitation of a male (pro-ceptivity), along with precopulatory vocalizations, in ovariecto-mized, estrogen-primed hamsters. These results showed that the effects of THC could be extended to other species and other sexual behaviors. Mani et al16 found that THC infused into the third ventricle of the rat brain enhanced lordosis. This effect was blocked by the cannabinoid antagonists SR141716A and SR144528. The endocannabinoid antagonists were found to block progesterone-induced lordosis, also. Mani et al further evaluated receptivity when progesterone and dopamine were blocked and showed that receptivity was inhibited. These results imply that THC-induced receptivity is mediated by dopamine and progesterone.

Selective endocannabinoid receptor agonists and antagonists have also been examined with regard to sexual responses in fe-male rodents. Memos et al17 carried out a series of experiments evaluating the effects of the endocannabinoid antagonist SR141716 and the effects of the endocannabinoid agonist AEA on partner preference when compared with a placebo in rats. Sexual motivation was measured by the number of visits the female rats made to the male rats. They showed that AEA enhanced sexual motivation as measured by more visits from the female rats, and SR141716 inhibited it. They also found that AEA and SR141716 did not affect lordosis. Zavatti et al18 had somewhat different results, finding that SR141716 inhibited lordosis but not motivation in female rats.

Not all animal studies have yielded similar results. Ferrari et al19 evaluated the effects of a potent cannabinoid receptor agonist, HU-210, in female rats and found that administration.

  Sexual motivation (runway test) Decreased Increased   Increased Decreased    
  Proceptivity(ultrasound vocalization or hops and darts) Increased   Increased    
    Receptivity (lordosis) Increased (low dose)Decreased(highdose)                    
    Increased Increased   Decreased Increased    
    Type of animal Simonsen Sprague-Dawley rats Golden hamsters Sprague-Dawley rats Long-Evans rats Long-Evans rats   Wistar rats Long-Evans rats Long-Evans rats    
Table1.Summaryofpreclinicalstudies Mechanism of action Agonist Agonist Agonist Antagonist Agonist   Agonist Antagonist/reverseagonist Agonist ¼¼AEAanandamide;THCtetrahydrocannabinol.  
  AuthorDrug Gordonetal(1978) TurleyandFloody(1980) Manietal(2000) Memosetal(2014) AEA   Ferrarietal(2000) Lopezetal(2009) Chadwicketal(2011)  
      THC THC THC SR141716     HU-210 AM-251 CP 55,940    
        15                  
      11   16 17     19 20 22    
                           

decreased both lordosis and the intensity of lordosis movements. The effect was dose and time dependent. Lopez et al20 evaluated receptivity, proceptivity, and sexual motivation as measured by a runway test. The runway test measures how fast a female rodent runs to a male rodent after being released from a chamber and is used as a surrogate for sexual motivation. They found that AM-251, an endocannabinoid antagonist/reverse agonist, enhanced these sexual behaviors. Lopez et al21 then evaluated a different cannabinoid receptor agonist, CP55,940, and found that sexual behaviors and motivation were decreased. Another study by Chadwick et al22 showed similar results with CP55,940. In rats, it decreased sexual motivation. Interestingly, female rats in this study showed no preference for a female or male mate when treated with CP55,940 but showed a male preference in the control group.

The varied findings in the animal studies likely reflect a series of factors. Different strains of animals, different types of agonist and antagonists, and different surrogate markers of sexual func-tion (proceptive vs receptive vs locomotor measures of motiva-tion) have been used. In addition, different compounds have different affinities for cannabinoid receptors. Routes of admin-istration are varied, as well (intracerebral vs systemic). Finally, the hormonal milieu in the animals varied among natural hormonal fluctuations, lack of hormones, or hormone replacement. Despite these limitations, animal studies provide some evidence that cannabinoids play a role in female sexual function, both directly and through interaction with the hypothalamic-pituitary-gonadal axis (Table 1).

Clinical Studies of the Effects of Cannabinoids on Female Sexual Function

Compared to the animal literature, there have been far more studies of the effect of marijuana on human female sexual function, although, to date, these findings have been limited to self-reported data. Despite the inability to conduct legal double-blind, randomized, placebo-controlled trials at this point in time in the United States, some data have been published to support the hypothesis that female sexual function is improved when women use marijuana in moderate doses.23e25 These studies are based on questionnaires, which are potentially fraught with bias.

Surveys of Males and Females Evaluating Effects of Marijuana Use on Sexual Function

In one of the earliest studies, the National Commission on Marihuana and Drugs23 reported findings from an informal survey of about 200 marijuana users who were asked, “Do you think being high on marijuana stimulates your sex interest, or not?” Among these 200 users, 44% reported “definitely increases their sexual desire, ” with 50% of those being women. They found that women were more likely than men to report an in-crease in desire. They also looked at rare, frequent, and heavy everyday marijuana use. Frequent but not daily marijuana use when compared to heavy everyday use and rare use (less than 1 joint a week) was associated with increased sexual pleasure in around 70% of users.

In 1974, Koff26 performed a survey of 251 college-aged stu-dents, who were asked about the amount of marijuana smoked each time the drug was used (1 joint or less, 2e4 joints, or more than 4 joints) and whether their sexual desire increased, decreased, or remained the same. He also asked whether sexual activity was more or less enjoyable after marijuana use. Of the 251 college students surveyed, 128 were female. The results of the survey indicated that 39.1% of males reported an increase in sexual desire, whereas 57.8% of females reported an increase—a significant difference (P ¼ .048). Also, 43% of the female participants re-ported heightened sexual pleasure. Additionally, Koff found that the effects of marijuana appeared to be dose dependent, noting that, although 71% of female participants reported increasing sexual motivation after 1 joint, the percentage of women reporting increased desire decreased after a larger consumption of marijuana (greater than 4 joints) (49.5%). This study supports the idea that the effect of marijuana on sexual function is dose dependent, such that low doses of marijuana (1 joint) can be sexually stimulating but high doses of marijuana can have the opposite effect.

In 1976, Chopra and Jandu27 interviewed 275 chronic marijuana users (smoked for 6 months to several years) from India and Nepal about the effects of marijuana and included some questions evaluating its effects on sexual function. This study observed similar dose-dependent effects and speculated that sexual inhibition is caused by an increased sedative effect seen at higher doses of marijuana intoxication. They did not divide their findings by gender.

A survey of 84 graduate students of health sciences in the southeastern United States was conducted by Dawley et al28 (78% male and 22% female). This survey included 57 multiple-choice and true/false questions that were developed to determine the attitudes of individuals regarding the effects of marijuana use on sexual function. The 84 graduate students were categorized as “experienced” (having had a sexual experience while under the influence of marijuana), “non-experienced” (those who have been under the influence of marijuana but have not concurrently had a sexual experience), and “non-smokers.” The study found that the “experienced participants” reported increased sexual pleasure (88%), sensations (48%), and satisfac-tion when both partners used marijuana (76%), as well as an increase in the intensity of the orgasm (58%). However, this study did not explore any differences between males and females, specifically.

These findings were further replicated in a 1982 survey done by Halikas et al.29 One hundred regular marijuana users (37 female users) with an average smoking experience of 2 years were systematically interviewed to assess the psychosocial effects of marijuana use, including effects on sexual function. This study demonstrated that 76% of females reported an increase in sexual pleasure and satisfaction (14% of women reported variable feelings), and 63% of women reported feelings of emotional

closeness and intimacy. Additionally, 32% of women reported an enhanced quality of orgasm, and the other 8% and 60% reported variable or no effects, respectively. Overall, 81% of people (men and women) reported pleasure-enhancing effects associated with marijuana use.

Data by Green et al30 support the previous finding by Halikas et al. Their review showed that approximately half of marijuana users reported increased aphrodisiac effects from marijuana use. Among regular marijuana users, 25% of them used marijuana in preparation for sexual intercourse. Of these users, over half re-ported increased sexual desire.

In 2004, Johnson et al31 conducted a survey-based, commu-nity epidemiological sample looking at the incidence and prev-alence of sexual dysfunction in the general population (inhibited orgasm, functional dyspareunia, inhibited sexual excitement, and inhibited sexual desire). Out of the 3,004 participants, 60% were female. After controlling for multiple variables such as de-mographics, health status, and psychiatric comorbidities, mari-juana was found to be associated with inhibited orgasm, as well as inhibited sexual excitement and desire. As opposed to the other studies mentioned in this review, Johnson et al asked survey questions specifically about sexual dysfunction, as opposed to general sexual function, and about comorbid drug and alcohol use. They did not ask questions about the potential benefits or experiences of marijuana usage, which perhaps played a role in why their results suggest a negative effect from marijuana.

Sumnall et al32 surveyed 281 sexually active volunteers regarding the effects of alcohol and drugs on their sexual be-haviors; 131 (48.5%) of the volunteers were female. The most commonly reported drug used was marijuana (46.9%), although some individuals reported mixing alcohol with drugs. Their study reported that both marijuana and ecstasy were more frequently taken to improve the sexual experience than alcohol. Those who had taken illicit drugs reported greater sexual plea-sure, increased mental/interpersonal contact with their sexual partner, greater willingness to sexually experiment, and a more satisfying sexual experience overall, indicating a greater total scale score for sex on drugs compared to alcohol (z ¼ 5.696; P <

.001). Although Sumnall et al found that it was not possible to distinguish the effects of different specific drugs, the overall effect was a more positive sexual experience on illicit drugs, including marijuana, compared to consuming alcohol.

In 2018, Palamar et al24 evaluated self-reported sexual effects of marijuana, ecstasy, and alcohol use in a group of 679 men and women (ages 18e25); 38.6% of the respondents were women. When focusing on marijuana users, both male and female, the majority reported increased sexual enjoyment (53.5%), orgasm intensity (44.9%), sexual intensity (61.8%), body sensitivity (49.1%), and either an increase (31.6%) or no change (51.6%) in sexual desire. Although this study did not specifically analyze male and female differences, the authors did note that females in their survey were more likely than men to report sexual

dysfunction (30.6%), which was defined for survey takers as “vaginal dryness,” after marijuana usage. They also noted that this definition of sexual dysfunction was limited and that par-ticipants may have experienced other forms of sexual dysfunction.

Female-Only Surveys Evaluating the Effects of Marijuana Use on Sexual Function

Sun and Eisenberg33 surveyed 28,176 women via household laptops in 2002, 2006e2010, and 2011e2015. Women were asked, “Now please think about the past 4 weeks. How many times have you had sexual intercourse with a man in the past 4 weeks?” This was followed by, “During the past 12 months, how often have you smoked marijuana?” with the choice of responses being never, once or twice during a year, several times during the year, approximately once a month, approximately once a week, or at least once a day. They found that a higher frequency of marijuana usage was associated with increased sexual frequency. Although association does not imply causation and potential confounders existed in this study, including the exclusion of homosexual encounters and acknowledgment that those who use marijuana regularly might already be psychologically more dis-inhibited in general compared to those who do not use, the authors suggested that marijuana’s impact on and potential benefit for sexual function should be further studied.

25 conducted a survey of 373 women from 2016 to 2017 to evaluate women’s perceptions of the effect of marijuana usage before sexual activity. Of the 373 women, 127 reported using marijuana before sex. The majority of women reported increases in sex drive, improvement in orgasm, and a decrease in pain. Specifically, women who reported regular marijuana usage before sexual activity had 2.13 higher odds of reporting satis-factory orgasms. Women with frequent marijuana usage had 2.10 times higher odds of satisfactory orgasms than those with infrequent usage.  observed that there appears to be a link between marijuana usage and satisfaction with orgasm, as well as with improvements in other domains of sexual function, a better understanding of which may lead to the development of treatments for female sexual dysfunction.

Serum Endocannabinoid Levels and Sexual Function

In 2012, Klein et al5 chose a more direct method of studying the endocannabinoid system and its effects on female sexual function. Their aim was to measure circulating endocannabinoid concen-trations in relation to subjective and physiological indices of sexual arousal in women. They measured physiological sexual arousal with vaginal photoplethysmography, specifically measuring vaginal pulse amplitude, which reflects phasic changes in vaginal engorgement with each heartbeat. The overall concept is that higher amplitudes indicate greater genital engorgement. Endo-cannabinoid concentrations (AEA and 2-arachidonoylglycerol) in 21 healthy premenopausal women were measured immediately

prior to and following viewing of both neutral and erotic films. Results indicated that increases in both physiological and subjec-tive measurements of sexual arousal were associated with signifi-cant decreases in levels of endocannabinoids. These findings support the hypothesis that the endocannabinoid system is involved in female sexual functioning and may well be inhibitory (Table 2).

DISCUSSION

Based on the above review of the literature, the most common sexual domains that have been evaluated include arousal, desire or “libido,” orgasm, pleasure, dyspareunia, vaginal lubrication, and duration of intercourse. Several studies have evaluated the effects of marijuana on libido, and it seems that changes in desire may be dose dependent. Studies support that lower doses

improve desire but higher doses either lower desire or do not affect desire at all.23,26,27

When evaluating sexual pleasure, most studies show that marijuana has a positive effect.27,30,31 Marijuana use with sex has

also been associated with prolonging orgasm or improving the quality of orgasm.5,24,34 Only 1 study that we reviewed reported

that marijuana use inhibits orgasm31; however, that study spe-cifically looked at dysfunction as opposed to overall function. Although our search revealed no articles that found an associa-tion between marijuana use and vaginal lubrication,35,36 this does not rule out such an effect, or an effect on vaginal blood flow, especially with a peripheral application.

Limitations

The body of evidence evaluating the effects of marijuana on female sexual function has several limitations. Although animal studies provide some information, there are no double-blind, randomized, placebo-controlled human trials from which to form a conclusion. The available human studies rely on recall and questionnaires. They are also quite different from each other. No validated questionnaires have been used, making it difficult to compare the results. Moreover, the specific wording of the ques-tions regarding libido, orgasm, pleasure, and pain all differed in both content and positive or negative valence. Some studies used questionnaires, and some used interviews. Some focused on marijuana users specifically, whereas others focused on a general population. Populations ranged from university students to pa-tients in an obstetrics and gynecology practice. Most studies focused on sexual function, but a single study evaluated potential sexual dysfunction. No human studies were able to evaluate the exact dose or timing of use. It is therefore difficult to make broad generalizations about the effects of marijuana on female sexual function based on available evidence.

It must be noted here that the other cannabinoids in mari-juana have not been tested empirically with regard to their effect on the sexual behavior of female rats or humans, although a recent study by Carvahlo et al37 reported an overall decrease

Table 2. Summary of clinical studies

  Author Type of marijuana usage Gender Sexual desire Sexual pleasure Other findings
  US Commission on Rare vs frequent vs heavy Male and female (200 Definite increase in sexual Frequent, but not every
  Marihuana and   participants) desire reported by   day, marijuana use
  Drug Abuse (1972)23     44% (44, or 50%, of   (compared to usage
        whom were female)   every day) was
            associated with
            increased sexual
            pleasure in 70% of
            users
  Koff (1974)26 One joint or less vs 2e4 Male and female (251 Increase in sexual desire Heightened sexual Effects of marijuana
    joints vs >4 joints participants; 128 noted by 57.8% of pleasure reported by appeared to be dose
      females) females 43% of female dependent; 71% of
          participants female participants
            reported increasing
            sexual motivation
            after 1 joint, but this
            percentage decreased
            after greater
            consumption (>4
            joints) to 49.5%
  Chopra and Jandu Chronic cannabis users Male and female (275 Dose-dependent effects
  (1976)27 (smoking 6 mo to several participants)     with marijuana similar
    years)       to the findings by Koff
  Dawley et al (1979)28 Experienced (having had sex Male and female (84 Increased sexual pleasure Increased sensations
    while under the influence participants)   reported by 88% of (48%)
    of marijuana)     participants Increased satisfaction
    vs non-experienced       with both partners
    (under the influence but       using (76%)
    no sexual experience) vs       Increase in the intensity
    non-smokers       of orgasm (58%)
  Halikas et al (1982)29 Average smoking experience Male and female (100 Increase in sexual 63% of women reported
    of 2 y participants; 37   pleasure and emotional closeness
      females)   satisfaction reported and intimacy
          by 76% of females  
          Overall, 81% of 32% of women reported
          participants reported an enhanced quality of
          pleasure-enhancing orgasm
          effects  
  Green et al (2003)30 Male and female Increased sexual desire
      participants reported by w50%    
            (continued)
Author Type of marijuana usage Gender Sexual desire Sexual pleasure Other findings
Johnson et al (2004)31 Marijuana usage and Male and female (3,004 Inhibited desire Inhibited orgasm and
  comorbid alcohol/drug participants; 60%     sexual excitement
  usage female)      
Sumnall et al (2007)32 Marijuana usage and Male and female (131 Increased sexual pleasure Increased mental and
  comorbid drug usage participants; 48.5%     interpersonal contact
    female)     with sexual partner
        Increased satisfaction Greater willingness to
        with sexual experience sexually experiment
Klein et al (2012)5 Measured circulating serum Increases in both
  endocannabinoid       physiological and
  concentrations       subjective
          measurements of
          arousal, which were
          associated with
          decreases in serum
          endocannabinoids
Sun and Eisenberg Never, once or twice a year, Female Higher frequency of
(2017)33 several times a year, once       marijuana usage
  a month, once a week,       associated with
  or at least once a day       increased sexual
          frequency
Palamar et al (2018)24 Marijuana, ecstasy, and Male and female (679 Increase or no change in Increased sexual 44.9% reported
  alcohol participants; 38.6% sexual desire reported enjoyment reported by increased orgasm
    women) by 31.6% 53.5% intensity
          30.6% of women
          reported sexual
          dysfunction (vaginal
          dryness)
 (2019)25 Regular or frequent Female Increase in sex drive 2.10 times higher odds of
  marijuana usage   reported by majority of   satisfactory orgasm
      women   with frequent
          marijuana usage; 2.13
          times higher odds
          with regular marijuana
          usage

fertility in female Swiss mice. It is also the case that the THC and cannabidiol content differs dramatically in different strains of marijuana,38 particularly in the marijuana that has been used legally in research, relative to strains consumed recreationally.39 This makes it impossible both quantitatively and qualitatively to compare the effects of laboratory-based intoxication with studies that examine retrospective experiences.

Clinical Implications

A better understanding of the role of the endocannabinoid system in female sexual function has important clinical impli-cations. Sexuality is complex, and the ECS is only one small part of it. A clearer understanding may lead not only to the devel-opment of therapeutic options for women but also to a deeper understanding of the mechanisms involved in sexuality. With increasing legalization, there is the potential to carry out more rigorous trials evaluating the exact dosing and timing of use as opposed to using recall. This may lead to more substantive conclusions than the animal and human studies have allowed us thus far.

Conflict of Interest: None.

Funding: None.

STATEMENT OF AUTHORSHIP

Category 1

  • Conception and Design

Becky Lynn; Amy Gee; Luna Zhang

  • Acquisition of Data

Becky Lynn; Amy Gee; Luna Zhang; James G. Pfaus

  • Analysis and Interpretation of Data

Becky Lynn; Amy Gee; Luna Zhang; James G. Pfaus

Category 2

  • Drafting the Article

Becky Lynn; Amy Gee; Luna Zhang; James G. Pfaus

  • Revising It for Intellectual Content

Becky Lynn; Amy Gee; Luna Zhang; James G. Pfaus

Category 3

  • Final Approval of the Completed Article

Becky Lynn; Amy Gee; Luna Zhang; James G. Pfaus

CONCLUSION

Female sexuality is a complex interplay of environmental, psychological, and physiological processes. Multiple neurotrans-mitters and hormones play a role in sexual excitation and inhi-bition. The information we have is limited to rodent studies and questionnaires that rely on memory, with none of the human studies yet being capable of delineating dose, timing, or other objective measures. Although there appears to be a dose de-pendency that separates putative excitatory effects from inhibi-tory effects on female sexual desire, orgasm, and reproductive function, and frequency of use also plays a role, it is not clear to what extent the psychoactive properties of the various cannabi-noids play a role. For example, it is possible that the sedative hypnotic properties of THC and tetrahydrocannabivarin at low doses disinhibit sexual desire and arousal in response to erotic cues, but perhaps this occurs to a large extent in women who experience anxiety about sex or other interpersonal interactions. With recent decriminalization in México, and legalizations in Canada and certain US states, the Northern Hemisphere is now ripe to develop the high-quality, evidence-based studies necessary to answer important questions regarding marijuana and female sexuality. Like any drug, marijuana has risks and side effects and should be used with that in mind. A compre-hensive understanding of the effects of marijuana and its con-stituent cannabinoids on female sexual function remains to be elucidated.

Corresponding Author: Becky Lynn, MD, Department of Obstetrics, Gynecology and Women’s Health, Division of General Obstetrics and Gynecology, Saint Louis University School of Medicine, St. Mary’s Hospital, 6420 Clayton Rd., St. Louis, MO 63117; E-mail: beckyklynn@gmail.com

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