Human T-lymphotropic virus 1 (HTLV-1) is a member of human Retroviridea, infects TCD4+in vivo. Although a small fraction (3–5%) of infected individuals may develop HTLV-associated myelopathy-tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL) over a lengthy period, most infected carriers remain asymptomatic (Bangham, 2000; Gessain and Cassar, 2012). HAM/TSP is a chronic inflammatory neurodegenerative disease in which HTLV-1-specific TCD4+ and TCD8+ lymphocytes cause demyelination in the central nervous system (Mozhgani et al., 2019) Meanwhile, ATLL is an aggressive malignancy of TCD4+ lymphocytes. ATLL is an aggressive malignancy of TCD4+ lymphocytes (Ahmadi Ghezeldasht et al., 2023; Bangham, 2023). The main clinical manifestations of HAM/TSP, as a chronic neuro-inflammatory spinal cord disease, are progressive spasticity, pain, and bladder disturbance (Ariaee et al., 2023; Yamauchi et al., 2021).

HTLV-1 is prevalent in the southwest of Japan, the Caribbean Sea, South America, Sub-Saharan Africa, and the Middle East (Gessain and Cassar, 2012). In Iran, some parts are endemic for this virus, including Razavi Khorasan, North Khorasan, West Azarbaijan, Ilam, Hormozgan, Tehran, Alborz, and Bushehr (Hedayati-Moghaddam et al., 2015; Rafatpanah et al., 2011).

New findings suggested that inflammatory reactions and the inappropriate host immune response to HTLV-1 virus can play pivotal role in HAM/TSP disease, particularly to trans-activator protein (Tax) and HTLV-1 basic leucine zipper factor (HBZ) (Ahmadi Ghezeldasht et al., 2023; Nozuma et al., 2020; Tarokhian et al., 2017). Tax and HBZ are regulatory factors in HTLV-1 replication, deterioration of the host immune system, and inducing malignancy (Ahmadi Ghezeldasht et al., 2023; Enose-Akahata et al., 2017; Matsuoka and Green, 2009). The main activities of these regulatory factors in the nucleus or cytoplasm of infected cells are still too controversial. The presence and localization of Tax and HBZ in TCD4+ infected cells in asymptomatic careers (ACs), ATLL and HAM/TSP patients were proved. Furthermore, they strongly affect the manifestations of the mentioned diseases (Baratella et al., 2017; Forlani et al., 2021; Raval et al., 2015). Tax is the main transcription factor in virus replication and inducing auto-proliferation of infected TCD4+ cells. On the other hand, Tax is an immunodominant antigen recognized by HTLV-1-specific cytotoxic CD8+T-cells (CTLs) (Melamed et al., 2015; Tanaka et al., 2022). These virus-specific CTLs, infiltrating CNS lesions, produce proinflammatory cytokines and indicate degranulation activity, leading to demyelination of the neurons in CNS (Tamaki et al., 2023; Yamano and Sato, 2012). Therefore, such as multiple sclerosis (MS), this neuro-inflammatory disease is also an immunopathologic disorder. Furthermore, like MS, HAM/TSP is not directly life-threatening, but the progressive nature of this disease severely impacts the quality of life in the patients without any effective treatment (Kuroda et al., 1995; Olindo et al., 2006; Puccioni-Sohler et al., 2007).

Cannabinoids and cannabinoid-like combinations have vigorous activities in body homeostasis, particularly in the CNS and immune system (Suryavanshi et al., 2020). The endocannabinoid system including anandamide (AEA) and 2-arachidonic glycerol (2-AG) and their receptors, cannabinoid receptor type 1 and 2 (CB1–2R), selectively have important roles in the central nervous (CNS) and immune systems (Kasatkina et al., 2021). For example, CB1R, as an anti-inflammatory mediator, plays essential activities in the equilibrium between inflammatory and anti-inflammatory agents in the CNS (Kendall and Yudowski, 2016). These properties may cause human beings applying the extracts of Cannabis sativa as drugs and medications. The ancient uses of herbal Δ9-tetrahydrocannabinol (THC) as the principal psychoactive agent in marijuana have led to considerable growth in the physiological and pathological study of cannabinoids, that may call Panacea (Nagarkatti et al., 2009). It is notable that cannabis may alter the balance between T-helper 1 (Th-1) and Th-2 cells in the response, by decreasing the production of cytokines caused by Th-1 cells and boosting the expression Th-2 cells induced cytokines (Klein, 2005).

Identifying human cannabinoid receptors and their functions in health and disorder has been one of the most notable biochemical and pharmacological discoveries in the last decades. Since the endocannabinoid system is crucial for the homeostasis of several biological processes, pathological conditions such as cardiovascular, neurological, metabolic, and immunological diseases are often associated with alterations of endocannabinoid tone (Haspula and Clark, 2020).

Cannabinoids are a group of compounds that mediate their impacts through cannabinoid receptors. CB1R is predominantly expressed in the brain, while CB2R is primarily found on the surface of immune system cells (Nagarkatti et al., 2009). In general, it seems that neurologic effects are linked to the CB1R, whereas their immunomodulatory activities are predominantly mediated through the CB2R (Benito et al., 2008; Turcotte et al., 2016).

In recent years, the cannabinoid system has drawn much interest in immune-pathological illnesses of the nervous system like MS (Mecha et al., 2020; Zajicek et al., 2005). Therefore, it was crucial to look into how these biological components may contribute to nervous system inflammatory disorders (Zou and Kumar, 2018). Therefore, medications for immune-degenerative and autoimmune diseases based on cannabinoids are developed, approved, and available in many developed countries in North America and many European countries for MS spasticity and pain. For example, Nabiximols (trade name Sativex) is approved for spasticity in the USA, Canada, and around 21 European countries (Abuhasira et al., 2018; Krcevski-Skvarc et al., 2018; Rainka et al., 2023). Nabiximols contain an equal quantity of THC and Cannabidiol (CBD) (Pagano et al., 2022; Russo, 2008).

Since the clinical and immune-pathological between HAM/TSP and MS are fairly similar, and the cannabinoid medications for spasticity and pain were approved, this study was conducted to investigate the host cannabinoid receptors and HTLV-1-host interaction host by assessing the HTLV-1 viral load, Tax, and HBZ regulatory factors. Since cannabinoids for MS may also be applied in HAM/TSP.