After the Billion-Dollar Psychedelic Bet: Who’s Next for Big Pharma?

When AbbVie wrote a $1.2 billion cheque for Gilgamesh Pharmaceuticals’ Bretisilocin, it wasn’t just buying a drug, it was buying a future.

That future, once dismissed as fringe science, is now being reframed as one of the most promising frontiers in modern psychiatry: psychedelic-inspired therapeutics that heal the brain not through serotonin tweaks, but by rebuilding neural architecture itself.

The deal marked a seismic shift, Big Pharma’s first full step into a field it had tiptoed around for years. But if Bretisilocin was the starter pistol, the race is now wide open.

The next generation of biotechs isn’t chasing the trip; they’re engineering it out entirely.

In the wake of Gilgamesh’s billion-dollar exit, a new wave of companies is emerging, smaller, stealthier, and far more scientifically disciplined than their first-wave predecessors.

Their mission: harness the therapeutic plasticity of psychedelics without the hallucinogenic side effects that complicate scalability, reimbursement, and patient access.

At the center of this movement are Enveric Biosciences and Equulus Therapeutics, two companies with very different paths, but a shared destination: mainstream adoption.

Enveric Biosciences (NASDAQ: ENVB) has been quietly re-architecting the psychedelic molecule from the inside out.

Its lead candidate, EB-003, is a non-hallucinogenic derivative of DMT — a compound famous for inducing intense, minutes-long hallucinations. Enveric’s version is designed to preserve the brain-healing plasticity without triggering the psychoactive cascade that makes DMT impractical in a clinical setting.

In preclinical studies, EB-003 shows promise in reducing anxiety and depression in animal models while maintaining oral bioavailability, a critical feature for pharma partners eyeing real-world scalability.

Behind the science sits the company’s Psybrary™ discovery platform, a massive molecular library mapping 5-HT receptor interactions to design selective neuroplastogens. In plain terms, it’s a psychedelic chemistry engine, and it’s already producing differentiated drug candidates.

As one analyst recently noted,

“If AbbVie was willing to pay $1.2 billion for a short-acting 5-HT₂A modulator, Enveric’s precision-engineered DMT analog may be the next logical move.”

With IP protection across the U.S., Europe, and Asia, and a growing focus on non-hallucinogenic mechanisms, Enveric isn’t competing with psychedelics anymore. It’s redefining them.

While Enveric builds out its DMT-derived portfolio, Equulus Therapeutics has taken a stealth-first approach — operating under the radar until now. But insiders are paying attention.

Equulus’ pipeline includes:

A 5-HT releaser (MDMA analog) — a non-dissociative, empathy-enhancing compound designed to deliver MDMA’s therapeutic benefits without neurotoxicity or euphoria.

A non-psychedelic 5-HT hybrid — engineered for durable mood stabilization.

A non-hallucinogenic ibogaine analog (EQL-101) — targeting addiction and depression with ibogaine’s regenerative neurochemistry but none of its cardiac risk.

And a confidential intranasal therapeutic already finalizing IND-enabling studies.

Preclinical work is being funded by the U.S. National Institute on Drug Abuse (NIDA) at RTI International, a signal of scientific rigor and government validation rarely seen in the psychedelic space.

If Gilgamesh was the proof that Big Pharma will pay for clean pharmacology, Equulus looks like the blueprint: a CNS-focused team, non-psychedelic chemistry, and government-backed data, all wrapped in a pharma-ready package.

Beyond Enveric and Equulus, the psychedelic-inspired therapeutics landscape is maturing fast and the dealmaking potential is obvious.

Delix Therapeutics continues to lead in non-hallucinogenic psychoplastogens, its platform backed by Eli Lilly and others.

Cybin is advancing its deuterated psilocin analog (CYB003) through late-stage trials — one of the most clinically advanced in the space.

GH Research is developing an inhalable 5-HT modulator designed for ultra-rapid onset — a likely fit for acute suicidality.

Atai Life Sciences and Compass Pathways remain the largest umbrella companies, consolidating early-stage innovation and infrastructure that could attract pharmaceutical suitors seeking turnkey entry.

Even Big Pharma’s rivals are rumored to be exploring similar partnerships, from Bristol Myers Squibb to Johnson & Johnson, both looking for footholds in post-SSRI psychiatry.

For decades, psychiatry has been trapped in a loop — serotonin tweaks, marginal gains, and a global mental-health crisis that outpaced innovation. Psychedelic-derived compounds offer something radically different: biological reset mechanisms that rewire the brain’s architecture in days, not months.

The early data are breathtaking. The regulatory barriers are slowly lifting. And for companies like Enveric and Equulus, whose compounds are non-psychedelic in effect, the commercialization pathway looks smoother than any of the first-wave hallucinogens.

That’s what makes the post-Gilgamesh era so fascinating,  the next wave of deals won’t be about novelty, they’ll be about fit. Pharma doesn’t want to run “psychedelic clinics.” It wants plug-and-play molecules that fit existing infrastructure.

And those molecules are finally here.

AbbVie’s deal was the match. The fire now burns across the biotech landscape.

Companies like Enveric and Equulus, both rooted in rigorous medicinal chemistry and stripped of the cultural baggage that slowed their predecessors — are emerging as the most acquisition-ready targets in this rapidly heating market.

As one industry observer put it,

“AbbVie just priced the playbook. Everyone else is flipping to the same page.”

The psychedelic revolution may have started on the fringe, but the next wave — quieter, cleaner, and backed by serious science — is shaping up to be the most valuable movement in modern mental health.