By Marcello Cherchi, MD PhD
For patients
Marijuana and cannabis products can make people feel disequilibrium and cause or worsen tinnitus.
For clinicians
Overview
Marijuana (Cannabis sativa) contains many cannabinoid compounds, of which the best studied include tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). Cannabinoid receptors (CB1, CB2) are distributed throughout the central nervous system, including the audiologic and vestibular systems. Exogenously administered cannabinoids appear to have largely deleterious effects on vestibular and ocular motor function, and the majority of studies also report cannabinoids can cause or exacerbate tinnitus.
Introduction
Marijuana (Cannabis sativa) contains over a hundred types of cannabinoid compounds. Those about which the most research data are available include tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) (Guerra, Naidoo, Cacabelos 2022).
As of this writing, in the United States, marijuana is considered illegal under federal law, and in the medical context cannabis is classified as a schedule III drug. Many states have decriminalized the possession and use of marijuana. In 2023 the Department of Health and Human Services submitted a recommendation to the Drug Enforcement Agency that cannabis be reclassified from a schedule III drug to a schedule I drug.
Epidemiology
It has been estimated that 3% to 5% of the world population has at some point tried cannabis in some form, and that in the United States, roughly 1 in 7 to 1 in 8 people have done so (Anthony, Lopez-Quintero, Alshaarawy 2017). It has further been estimated that 10% of people who have tried a cannabis product have a cannabis use disorder (Connor et al. 2021).
Pathophysiological mechanism of disease
There are several cannabinoid receptors, including:
- CB1, encoded by the CNR1 gene at locus 6q15 (OMIM 114610)
- CB2, encoded by the CNR2 gene at locus 1p36.11 (OMIM 605051)
Animal studies have shown that cannabinoid receptors are distributed throughout the central nervous system, including in the audiovestibular system (Baek et al. 2008; Chi and Kandler 2012; Gong et al. 2006; Newsham-West, Darlington, Smith 1998; Trattner et al. 2013).
There are numerous endogenous cannabinoids. Of the exogenous cannabinoids, THC is an agonist at CB1 and CB2 receptors, while CBD is a non-competitive antagonist at CB1 and CB2 receptors (Guerra, Naidoo, Cacabelos 2022).
The mechanisms by which cannabinoids influence audiovestibular function is unknown. However, binding cannabinoid receptors has downstream effects on multiple neurotransmitter systems, including modulation of multiple G‑protein-coupled receptors, gamma aminobutyric acid, glutamate and inflammatory pathways, many of which are present in audiologic and vestibular pathways. Thus, it should not be surprising that cannabinoids can have audiovestibular effects.
Clinical presentation
Of people who seek medical care for complications from cannabis use, the most common otology-related complaints are disequilibrium, hearing loss and tinnitus (Phulka, Howlett, Hu 2021).
Ocular motor examination
Kibby and Halcomb (Kibby and Halcomb 2013) reported the case of a 25-year-old male who presented with 3 days of visual disturbance and dizziness following marijuana use. They documented gaze-evoked nystagmus.
Pradeep and colleagues (Pradeep et al. 2008) reported the case of a 19-year-old male with congenital nystagmus who reported that smoking marijuana improved his vision. The investigators compared performance on dynamic visual acuity testing after the patient had smoked marijuana versus after 3 weeks of abstinence from marijuana, and found that visual acuity in the right eye improved by 3 LogMAR lines in the left eye and 2 LogMAR lines in the right eye. They also reported that the magnitude of the congenital nystagmus improved at various degrees of gaze eccentricity after the patient had smoked marijuana compared to after 3 weeks of abstinence.
Testing: auditory
Spector (Spector 1974) studied audiometry in 65 chronic marijuana users (61% males, age range 18 – 40 years, mean age 23 years) and 24 control subjects (41% males, mean age 28 years) and reported that, “No auditory differences were noted.”
Though not evident on standard audiometry, the effects of cannabinoids on tinnitus is controversial (see below).
Testing: vestibular
Spector (Spector 1973) studied the acute effects of marijuana versus placebo by electronystagmography in 72 users (age range 21 – 40 years) and reported, “Results indicated no vestibular effect” on sinusoidal tracking, spontaneous nystagmus, positional nystagmus, and rotation of torsional swing.
Spector (Spector 1974) studied electronystagmography in 65 chronic marijuana users (61% males, age range 18 – 40 years, mean age 23 years) and 24 control subjects (41% males, mean age 28 years) and reported that (1) a decrease in the maximum amplitude of torsional swing; (2) increased incidence of positional nystagmus; and (3) decrease slow phase velocity “on right warm and left and right cold calorics but not in the left warm [caloric] test.”
Schon and colleagues (Schon et al. 1999) reported the case of a 52-year-old male with clinically definite multiple sclerosis who had been suffering from dysconjugate elliptical pendular nystagmus. Using video oculography they compared the effect of placebo and two different doses of tetrahydrocannabinol, studying nystagmus and serum concentrations of tetrahydrocannabinol catabolites. They found a strong inverse correlation between serum concentrations of tetrahydrocannabinol catabolites and magnitude of nystagmus.
Treatment of symptoms resulting from cannabinoids
The mainstay of treatment for cannabis-related symptoms is detoxification.
Can cannabinoids treat otovestibular symptoms?
In the vestibular domain: Marijuana has been reported to help visual symptoms in one case report of congenital nystagmus (Pradeep et al. 2008) and two cases of pendular nystagmus related to multiple sclerosis (Dell’Osso 2000; Schon et al. 1999). Despite these case reports, the overall evidence is stronger that cannabinoids have adverse effects on the vestibular and ocular motor systems.
In the auditory domain: Some tinnitus patients report symptom relief with cannabis (Mavedatnia et al. 2023), but the preponderance of the evidence is that cannabinoids have no therapeutic effect on tinnitus (Narwani et al. 2020; Zheng and Smith 2019), and some research suggests that cannabinoids may cause or worsen tinnitus (Reyes Orozco et al. 2023).
Thus, we would agree with reviews that conclude the currently available evidence does not support a therapeutic role for cannabinoids in the management of otovestibular symptoms (Smith and Zheng 2016).
Notes
The reader should note that the above discussion is restricted to the relationship between cannabinoids and otovestibular symptoms. Cannabinoids have numerous effects on many other organ systems, including endocrine, hormonal, reproductive, genitourinary, cognitive, emotional, cardiovascular, gastrointestinal, hepatic, immunological and others.
References
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