Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective

Abstract

Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is affected also by anxiety, memory, and attention circuits where cannabinoid effects are well described. Available studies on animal models of tinnitus suggest that cannabinoids are not likely to be helpful in tinnitus treatment and could even be harmful. However, the pharmacology of cannabinoids is very complex, and most studies focused on neural CB1R-based responses. Cannabinoid effects on the immune system (where CB2Rs predominate) are increasingly recognized as essential in understanding nervous system pathological responses, and data on immune cannabinoid targets have emerged in the auditory system as well. In addition, nonclassical cannabinoid targets (such as TRP channels) appear to play an important role in the auditory system as well. This review will focus on neuroimmunological mechanisms for cannabinoid effects and their possible use as protective and therapeutic agents in the ear and auditory system, especially in tinnitus.

S3 Guideline: Chronic Tinnitus

“…In a recent review, connections between cannabis effects and an influence on the immune response of the auditory system are presented and a potentially positive effect for tinnitus therapy is postulated, without, however, being able to draw on studies for this [ 247 ].…”

Potential effects of cannabinoids on audiovestibular function: A narrative review

“…Frontiers in Pharmacology frontiersin.org TABLE 1 (Continued) Profile of the different cannabinoids and drugs that act on the cannabinoid system that may be effective in the treatment of audiovestibular disorders. Weizman et al, 2018), and several other conditions (Kogan and Mechoulam, 2007;Perin et al, 2020;Khalsa et al, 2022). Since many of the above-mentioned and other nervous system disorders also affect the auditory and vestibular pathway, and are associated with dizziness, nystagmus and auditory symptoms, these molecules may help address several types of audiovestibular disorders.…”

“…In addition to the commercialization of cannabinoid-containing medications and supplements, several clinical studies are currently investigating the effects of 1) synthetic cannabinoid-derived drugs (CB1/CB2 receptor agonists/antagonists), and 2) non-cannabinoid-derived compounds (MAGL/FAAH inhibitors) that belong to a part of a different class of biologically active molecules, that regulate the EC system. These compounds have been used in clinical trials and observational studies to manage treatment-resistant epilepsy ( Devinsky et al, 2016 ), ALS (amyotrophic lateral sclerosis) ( Weber et al, 2010 ), MS (multiple sclerosis) ( Collin, Davies, Mutiboko and Ratcliffe, 2007 ; Zajicek et al, 2012 ), Alzheimer’s disease ( Herrmann et al, 2019 ), schizophrenia ( Leweke et al, 2012 ; McGuire et al, 2018 ), acute and chronic pain ( van de Donk et al, 2018 ; Weizman et al, 2018 ), and several other conditions ( Kogan and Mechoulam, 2007 ; Perin et al, 2020 ; Khalsa et al, 2022 ). Since many of the above-mentioned and other nervous system disorders also affect the auditory and vestibular pathway, and are associated with dizziness, nystagmus and auditory symptoms, these molecules may help address several types of audiovestibular disorders.…”

Cannabis use amongst tinnitus patients: Consumption patterns and attitudes

“…Cannabis is one of the most commonly used drugs in North America, with close to half of Canadians aged 15 or older having reported using it [19]. Cannabinoids can modulate hyperexcitability, are involved in protection of auditory damage, neural processing in the auditory system, and in non-auditory circuits associated with tinnitus [20]. It has been used in treatment of neuropathic pain, anxiety, depression, headaches and seizures, all of which have similarities or associations with tinnitus [21][22][23].…”

“…It has been used in treatment of neuropathic pain, anxiety, depression, headaches and seizures, all of which have similarities or associations with tinnitus [21][22][23]. With its legalization in various nations, it has been considered as a potential treatment for tinnitus, with several tinnitus sufferers turning to it as a possible remedy [20]. Limited research exists regarding the use of cannabis as a therapeutic agent among the tinnitus patient population.…”