Opioid-induced Hallucinations: A Review of the Literature, Pathophysiology, Diagnosis, and Treatment

Abstract

Despite their association with multiple adverse effects, opioid prescription continues to increase. Opioid-induced hallucination is an uncommon yet significant adverse effect of opioid treatment. The practitioner may encounter patient reluctance to volunteer the occurrence of this phenomenon because of fears of being judged mentally unsound. The majority of the literature concerning opioid-induced hallucinations arises from treatment during end-of-life care and cancer pain. Because the rate of opioid prescriptions continues to increase in the population, the rate of opioid-associated hallucinations may also conceivably increase. With a forecasted increase in the patient-to-physician ratio, opioid therapy is predicted to be provided by practitioners of varying backgrounds and medical specialties. Hence, knowledge of the pharmacology and potential adverse effects of these agents is required. This review seeks to increase awareness of this potential complication through a discussion of the literature, potential mechanisms of action, diagnosis, and treatment strategies.

Hydromorphone-Induced Tactile Hallucinations: Rare Opioid Side Effect

“…In some cases, patients feel uncomfortable speaking-up about experiences for fear of being considered psychologically unstable [4,5]. There are citations reporting opioid hallucinations, mostly auditory and visual, but rarely of the tactile nature that our patient experienced [4]. As far as we are aware, there is no report of this phenomenon in association with hydromorphone.…”

“…Opioid-induced hallucinations are an uncommon but significant adverse effect, which may be attributed to underlying psychiatric disease and consequently be under-reported, rather than recognized as side effects of the opioid itself. In some cases, patients feel uncomfortable speaking-up about experiences for fear of being considered psychologically unstable [4,5]. There are citations reporting opioid hallucinations, mostly auditory and visual, but rarely of the tactile nature that our patient experienced [4].…”

The Pharmacology of Visual Hallucinations in Synucleinopathies

“…The modulation of glutamatergic or opioid neurotransmitters is also involved in VH (Niesters et al, 2012;Sivanesan et al, 2016) but the exact activity of these systems is still largely unexplored. In summary, the neuropharmacology of VH is a fascinating and still "under construction" chapter of clinical neuroscience.…”

“…The opioid system is mostly involved in the regulation of pain perception (Al-Hasani and Bruchas, 2011;Stein, 2016;Valentino, 2018). Several observations have also indicated a role for opioids in the induction of VH (Sivanesan et al, 2016;Tan and Gan, 2016), although only a few studies have so far dissected the mechanisms underlying the psychoactive properties of the compounds. Early reports have associated the hallucinogenic properties of opioids with the activation of σ receptors (Sivanesan et al, 2016).…”

“…Several observations have also indicated a role for opioids in the induction of VH (Sivanesan et al, 2016;Tan and Gan, 2016), although only a few studies have so far dissected the mechanisms underlying the psychoactive properties of the compounds. Early reports have associated the hallucinogenic properties of opioids with the activation of σ receptors (Sivanesan et al, 2016). However, the σ receptor is no longer considered an opioid receptor (Hayashi and Su, 2005) because it is bound by different classes of psychotropic drugs as well as by sexual hormones, haloperidol, and other substances (Hayashi and Su, 2005).…”