Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population. Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating transient receptor potential vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability. Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death. Acute myeloid leukemia (Aml-1) transcription factors play a pivotal role in GBM proliferation and differentiation and it is known that Aml-1 control the expression of several nociceptive receptors. So, we evaluated the expression levels of Aml-1 spliced variants (Aml-1a, b and c) in GSCs and during their differentiation. We found that Aml-1a is upregulated during GSCs differentiation, and its downregulation restores a stem cell phenotype in differentiated GSCs. Since it was demonstrated that CBD induces also TRPV2 expression and that TRPV2 is involved in GSCs differentiation, we evaluated if Aml-1a interacted directly with TRPV2 promoters. Herein, we found that Aml-1a binds TRPV2 promoters and that Aml-1a expression is upregulated by CBD treatment, in a TRPV2 and PI3K/AKT dependent manner. Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.
Keywords: Aml-1; autophagy; cannabidiol; chemosensitivity; differentiation; glioblastoma stem-like cells.
After that initial decline in which the disruptions caused by Covid may have played a part (both for MRBs and bank compliance teams), the numbers have shown no change. Those numbers, derived from a total of 170,975 SARs received by FINCEN, show an ongoing disconnect between a rapidly expanding industry and a financial system that is still somewhat reluctant to engage with it.
The main issue for many banks and credit institutions is the persistent Federal stance on marijuana as a controlled substance. Regardless of the legalization at the state level, marijuana’s status as a Schedule 1 substance means that banks have to classify MRBs as being involved in illegal acts in one form or another.
But the arrival of a new administration in Washington under the Democrats has significantly boosted chances of legalization of marijuana. A legalization bill has already been passed by the Democrat-controlled House in December 2020.
The compliance burden on banks dealing with MRBs
Let’s first address the more straightforward question on the impact of the pandemic on the legal marijuana industry.
But the legally defined “hemp” is a cannabis plant with low THC (unsuitable for the dope industry). As a result, the 2019 refresh could not have a significant impact on the pattern of financial institutional dealings with the marijuana industry.
Further, it would also allow big banks and other financial institutions to even consider MRBs as their customers. Given the resilience displayed by the industry during Covid, it should find no shortage of creditors. Everything hinges on legalization though – it remains to be seen how that will pan out in the next 12-18 months.
The impact of Covid-19 on cannabis
Driven by exceptional demand and growing support for legalization, the legal cannabis industry was valued at $13.2 billion in 2019. Investors poured close to $120 billion into marijuana-related businesses (MRBs) that year, as forecasts predicted a CAGR of 21% extending to 2022 and beyond.
While other retail businesses and sectors struggled to cope with the pressures of lockdowns and social distancing in 2020, the cannabis sector may have actually thrived. The single biggest reason has to be the very nature of the product the industry is selling.
Many financial institutions have remained hesitant to provide services to the hemp industry in the 18+ months since the 2018 Farm Bill, due in large part to the perceived burden of incorporating hemp-specific procedures into their AML Compliance Programs. The June guidance may alleviate that burden to an extent by providing additional clarity regarding an institution’s BSA/AML obligations when banking hemp. With many banks remaining on the sidelines, the rewards for those willing to serve the hemp industry could far exceed the costs.
On June 29, the Financial Crimes Enforcement Network (FinCEN) issued guidance (the “June guidance”) to “address questions related to Bank Secrecy Act/Anti-Money Laundering (BSA/AML) regulatory requirements” for providing banking services to hemp businesses. By its terms, the June guidance is “intended to enhance the availability of financial services for” hemp businesses – something that has been sorely lacking since hemp (i.e., cannabis containing less than 0.3% THC) was legalized at the federal level under the Agriculture Improvement Act of 2018 (the “2018 Farm Bill,” which we analyzed here).
The June guidance makes clear that financial institutions should tailor the customer risk profiles of and CDD for their hemp clients to reflect the unique aspects of the hemp industry. For example, when performing CDD on a hemp customer, a financial institution should verify the customer is complying with the licensing requirements of the jurisdiction in which it is operating. The June guidance states that an institution can “confirm [a] hemp grower’s compliance … by either obtaining (1) a written attestation by the hemp grower that they are validly licensed, or (2) a copy of such license.” Whether additional information is required “will depend on the financial institution’s assessment of the level of risk posed by” the customer. The June guidance provides the following examples of additional information a financial institution could seek: (1) crop inspection or testing reports; (2) license renewals; (3) updated attestations from the hemp customer; or (4) the customer’s correspondence with the applicable state, tribal, or federal licensing authority.
Suspicious Activity Reporting
Like the December guidance, FinCEN’s June guidance states that “financial institutions are not required to file a [SAR] on customers solely because they are engaged in the growth or cultivation of hemp in accordance with applicable laws and regulations.” Here, “solely” is the operative word – financial institutions still must utilize their customer risk profiles and ongoing CDD to determine whether their hemp customers are engaged in “suspicious activity” that warrants a SAR. The June guidance lists examples of such suspicious activity:
Hunter Robinson represents clients in commercial litigation and compliance-related matters across the country. His litigation practice focuses on representing financial institutions in lender-liability, title, and business disputes, including class actions. Hunter represents mortgage servicers and lenders in suits arising from repurchase demands, and…
Customer Due Diligence and Customer Identification Programs
Broadly speaking, the BSA requires that a financial institution establish an effective “AML Compliance Program,” comply with customer due diligence (CDD) and customer identification program (CIP) obligations, report certain currency transactions, and file a “Suspicious Activity Report” (SAR) when it detects a “known or suspected violation of Federal law or a suspicious transaction related to a money laundering activity or a violation of the [BSA].” In guidance issued on December 3, 2019 (the “December guidance,” which we analyzed here), FinCEN and other federal regulators clarified that financial institutions are not required to file a SAR regarding a hemp customer “solely because” the customer grows or cultivates hemp. The June guidance builds on the December guidance by (1) clarifying a financial institution’s CDD and CIP obligations with respect to its hemp customers, and (2) providing examples of “suspicious activity” that may prompt a financial institution to file a SAR regarding one of its hemp customers.
Jay Wright is a partner in the firm’s Banking and Financial Services and Litigation practice groups. Jay has earned his Accredited Mortgage Professional (AMP) designation through the Mortgage Bankers Association (MBA), and is one of a small number of lawyers who have achieved…