1. Introduction
Opium use disorder is a critical public health issue in Iran, accounting for 98% of the world's opium seizures (1). In response, Iran initiated a methadone and buprenorphine treatment program over two decades ago, yielding substantial success (2, 3). Buprenorphine, a synthetic derivative of thebaine and a partial agonist at the μ-opioid receptor and an antagonist at the κ-opioid receptor, offers a potent analgesic effect 25 to 40 times that of morphine, but with considerable cardio-respiratory tolerance considerations. It is employed both as a pain reliever in low doses and as a maintenance therapy in higher doses for opioid dependence (4, 5). The abuse potential of buprenorphine has been known since its clinical introduction (6). Data from multiple countries, including Finland, France, Great Britain, and Australia, indicate a persistent rise in buprenorphine abuse, often involving alternative administration routes such as intravenous and intranasal (7). Intranasal drug abuse can lead to severe nasal and respiratory complications, paralleling those seen with substances like heroin and cocaine (8, 9). Buprenorphine can be snorted nasally due to its pharmacological properties and potential for mucosal absorption (10). The combination of buprenorphine with naloxone aims to reduce intravenous abuse potential; however, the abuse of buprenorphine alone and in combination continues, as indicated by recent studies and reports from needle exchange programs (11). Among 111 surveyed individuals with a history of drug use in France, 36 patients (32%) reported intravenous use, 15 people (13.5%) sublingually, and 24 people (21.6%) had used it both intravenously and orally (12). In another study in Australia among 372 patients under medication-assisted treatment who used buprenorphine, it was reported that 65 of them (18%) had smoked or snorted buprenorphine at least once. Of these 65 buprenorphine inhalers, 50 clients had smoked buprenorphine (77%). Buprenorphine sniffing was less common, with less than 10% having experienced it, and there was no constant sniffing (13). The combination of buprenorphine and naloxone was introduced to prevent the non-sublingual use of buprenorphine. This combination was expected to have less abuse potential than buprenorphine alone. However, the abuse of buprenorphine by non-sublingual routes did not decrease significantly. This may be because combining naloxone with buprenorphine does not block all of its agonistic effects when administered non-sublingually. In contrast to this finding, respondents were willing to pay a significantly higher price for buprenorphine than for the combination product (7). In Iran, the prevalence of lifetime non-medical use of buprenorphine is reported to be 0.1%, and there are no reports of intranasal use of buprenorphine from Iran (14, 15). Among people with opioid use disorder (OUD), buprenorphine is the primary drug of abuse in less than 2% of people with OUD. Of these, more than 95% use it sublingually or intravenously, and less than 5% use it as their primary route of abuse intranasally. Given the low percentage of buprenorphine abusers among people with OUD, intranasal abuse of buprenorphine is an uncommon route. What has been concluded from past research is that abuse of buprenorphine from routes other than sublingual is seen mostly in people who have had a history of injection use (such as injecting heroin) or a history of intranasal use (such as cocaine snorting) (7, 10, 16, 17).
2. Case Presentation
This case report examines a 39-year-old male patient with a history of tramadol, opium, and methamphetamine use. He began taking tramadol occasionally at the age of 22 and started using opium at the age of 24. Over the last nine years, in addition to using opium, he has occasionally used methamphetamine. He has been undergoing maintenance treatment with buprenorphine for the past seven years, which he has been using intranasally for the past three years despite being introduced sublingually. During these seven years, he was withdrawn from treatment several times and used opium for several months. During the times he used opium, he also used methamphetamine. When he returned to treatment, he sometimes took buprenorphine sublingually and sometimes snorted it through the nose. For the last three years, he has exclusively snorted buprenorphine. During this period, he has occasionally used methamphetamine through inhalation and via a pipe.
This case highlights the severe physical consequences of chronic intranasal buprenorphine use, including nasal mucosa erythema, congestion, severe deviation of the nasal septum, and recurrent sinus infections. Visibly, the nose was deviated to one side. On intranasal examination, the mucosa was erythematous and congested, and the middle septum was severely deviated to the right. Additionally, in the upper part of the middle septum, there was a small area of atrophy and necrosis. According to the patient, the middle septum of his nose was perforated, as confirmed by an ENT specialist. The patient had a history of chronic sinusitis and recurrent attacks of acute sinus infections, as well as severe breathing problems during sleep. He had also experienced recurrent attacks of pneumonia in the last two years. The patient's current drug dose is 8 mg, which he snorts a 2 mg pill each time in four stages. He also consumes half a gram of methamphetamine 3 - 4 days a week. While he achieves the same result and effect sublingually, he forcibly snorts through his nose, and although he is aware of the severe complications and problems caused to his nose and airways, he cannot refrain from buprenorphine snorting.
3. Discussion
The possibility of absorbing buprenorphine via the sublingual route makes it suitable for abuse through respiratory routes, such as intranasal snorting. This is because it can be easily absorbed from the mucous membranes, and its continuous snorting, similar to the consumption of heroin and cocaine through the nose, leads to serious and irreversible injuries and complications. These include congestion and erythema of the nasal mucosa, particularly the middle septum, deviation of the nasal septum to one side, capping and blocking of one side of the nose, perforation of the middle nasal septum, frequent sinus infections, chronic sinusitis, severe breathing problems during sleep, and reduced sleep quality.
Buprenorphine's abuse through non-traditional routes, such as intranasal and intravenous, necessitates a reconsideration of current treatment practices and the formulation of strategies to mitigate these risks. The case study underscores the need for enhanced patient education, monitoring, and potentially reformulating medications to deter misuse while providing effective treatment for opioid dependence.
