New laboratory work shows neuropeptides — long neglected in favour of fast neurotransmitters — can act as primary messengers in distinct brain circuits for panic and fear, offering new drug and therapy targets for trauma-related disorders such as PTSD. Recent studies using novel genetically encoded sensors and circuit-specific manipulations identify a PACAP-driven panic pathway in the brainstem and peptide-dominated signalling in threat-learning circuits, while separate research implicates endocannabinoid action in stress-driven generalisation of fear memories. These advances explain why panic, conditioned fear and memory generalisation can behave differently, and point to concrete directions for Thai mental-health policy, clinical practice and research investment. ( Chemistry World feature: The chemistry of fear )
Fear and panic feel similar to the person suffering them, but the chemistry and circuits behind them are diverging into clearer view. Work from several groups shows that dense-core-vesicle peptides such as PACAP (pituitary adenylate cyclase-activating polypeptide) and orexins can carry the principal signal in particular pathways that control autonomic and behavioural aspects of panic and unconditioned aversive responses. In parallel, studies from another team show that endocannabinoid signalling can open the gate for more neurons to join a memory engram under stress, producing the vague, overgeneralised memories that underlie many PTSD symptoms. Together, these results create a new mechanistic map of fear that can be translated into Thai clinical priorities and public-health messaging. ( Chemistry World feature: The chemistry of fear )
Understanding why this matters to Thai readers begins with the burden of trauma and anxiety disorders in the country. Thailand faces mental-health pressures from natural disasters, accidents and the COVID-19 pandemic, and a sizable share of the population experiences anxiety or trauma-related symptoms that strain families and primary-care services. The World Health Organization country profile highlights ongoing mental-health needs in Thailand, while national reports and recent regional analyses document rising numbers of anxiety and stress-related conditions across ASEAN countries — trends that make mechanistic advances in fear biology relevant to public health planning and clinical practice here. ( WHO country profile — Thailand ) ( Lancet Public Health: Epidemiology and burden of ten mental disorders in ASEAN countries )
Key facts emerging from the new research show a surprising role for peptides in signalling danger. A 2024 Cell paper introduced two genetically encoded tools — a pH-sensitive vesicle sensor that lights up when peptide-containing large dense-core vesicles fuse, and a genetically encoded peptidase that degrades peptides inside vesicles to silence peptidergic transmission — and used them in behaving mice to map threat circuits. The authors reported that in the parabrachial-to-amygdalar threat pathway, neuropeptide release predominated over glutamate during unconditioned aversive events, and that silencing peptides disrupted threat learning even when glutamate signalling remained intact. This suggests that peptides can act as the primary transmitters encoding danger in at least some circuits. ( Presynaptic sensor and silencer of peptidergic transmission, Cell 2024 )
Separately, investigators at the Salk Institute and collaborators identified a PACAP-expressing population in the parabrachial nucleus that appears to drive panic-like physiological and behavioural states in mice. Activity in these PACAP-producing neurons rose during panic-inducing manipulations such as elevated CO2 exposure and pharmacological panic provocation, and optogenetic activation produced panic-like responses while inhibition reduced them. The team identified the PACAP receptor PAC1R as a downstream mediator, indicating a discrete peptide-dependent panic pathway that is anatomically and functionally distinct from conditioned fear circuits. Intriguingly, PACAP cell activity decreased during visually looming stimuli that evoke freezing, highlighting opposing peptide dynamics in panic versus certain forms of fear. ( A pontomesencephalic PACAPergic pathway underlying panic-like behaviour, PubMed/PMC (Salk collaboration) ) ( Salk Institute news release on PACAP panic pathway )
Historical peptide work also helps explain physiological facets of fear. Research on orexin (hypocretin) peptides, first linked to wakefulness and appetite, later found that orexin signalling drives heartbeat, breathing and pain modulation during threats. Studies in orexin-deficient mice show blunted autonomic and analgesic responses to fear, aligning with a model in which peptide systems scale physiological defence responses from wakefulness to full fight-or-flight. ( Chemistry World feature: The chemistry of fear )
On the memory side, a recent study from a Toronto-based team illuminates how acute stress causes memory overgeneralisation — a core problem in PTSD where traumatic memories lose detail and trigger fear in safe situations. The researchers showed that endocannabinoids act retrogradely to suppress parvalbumin-positive (PV+) interneurons in the lateral amygdala, effectively loosening inhibitory control that normally limits which neurons join an engram. Under stress, this “velvet rope” is opened, producing denser, less specific engrams and widespread fear responses; blocking endocannabinoid synthesis or boosting PV+ interneuron activity restored memory specificity in mice. This mechanism offers an explanation for why stress can make fear memories vague and pervasive. ( Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice, Cell/Jan 2025 )
Experts interviewed and quoted in the reporting emphasise both the promise and the caveats. A senior neuroscientist specialising in memory described the generalisation effect as an adaptive but overzealous protective mechanism that becomes pathological when unchecked, noting the importance of new molecular tools in revealing these processes (quote reproduced from the Chemistry World feature). A peptide researcher underscored the technical breakthrough of a vesicular pH sensor that made direct peptide-release measurements possible and said without such tools the peptidergic role would have remained obscured (Chemistry World; original papers cited above). These voices point to a consensus: the chemistry of fear is more molecularly diverse than previously appreciated, and the diversity matters for treatment design. ( Chemistry World feature: The chemistry of fear ) ( Presynaptic sensor and silencer of peptidergic transmission, Cell 2024 )
For Thailand, the clinical implications are concrete. First, recognising that panic attacks and conditioned fear may arise from different molecular drivers supports more tailored treatments rather than one-size-fits-all anxiety care. PACAP–PAC1R signalling and orexin pathways point to candidate drug targets for panic symptoms that involve intense autonomic arousal, while peptide-dependent threat encoding and endocannabinoid-modulated engram expansion suggest different pharmacological or neuromodulatory strategies for trauma memory. Second, the finding that endocannabinoids can worsen memory generalisation under stress cautions against indiscriminate use of cannabis or cannabinoid-based therapies for PTSD — an especially relevant warning in countries where medical or recreational cannabis debates are active. Researchers in the field have already flagged mixed evidence for cannabinoids in PTSD, and the new mechanism helps explain why effects may vary. ( Chemistry World feature: The chemistry of fear ) ( Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice, Cell/Jan 2025 )
Thai cultural and historical contexts will shape how these scientific advances are applied. Family-based care, Buddhist practices that emphasise mindfulness and community resilience, and respect for authority shape help-seeking and treatment adherence in Thailand. Public-health campaigns can frame new treatments and screening around family support, community clinics and culturally acceptable interventions such as mindfulness-based therapies that align with Buddhist values. At the same time, stigma around mental illness and variable access to specialised psychiatric services outside Bangkok mean that translating peptide-targeted drugs or novel psychotherapies into widespread benefits will require investment in primary-care training and telepsychiatry. Recent Thai research and reports document increasing mental-health needs among adolescents and workers after disasters and the pandemic, underlining the urgency of scalable responses. ( UNICEF Thailand mental-health country report ) ( WHO country profile — Thailand )
Looking ahead, the science suggests several likely developments. Pharmaceutical efforts may advance small-molecule or biologic modulators of peptide receptors (for example, PAC1R antagonists) or orexin signalling, and new clinical trials could test whether these agents reduce panic symptoms or autonomic hyperarousal. Parallel translational work will be needed to determine how peptide-dominant signalling in mice maps onto human brain circuits, and whether biomarkers (imaging, peripheral peptide measures) can identify which patients will benefit. On the memory side, interventions that stabilise PV+ interneuron function or limit stress-driven endocannabinoid signalling during or shortly after trauma might reduce harmful generalisation; these ideas could inform early interventions after disasters. Importantly, any pharmacological approach must be combined with evidence-based psychotherapies for PTSD — such as trauma-focused cognitive behavioural therapy and exposure-based treatments — to address both biology and learned behaviour. ( Presynaptic sensor and silencer of peptidergic transmission, Cell 2024 ) ( Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice, Cell/Jan 2025 )
Practical, actionable steps for Thailand follow directly from these findings. Health authorities should prioritise training primary-care clinicians in recognizing the clinical differences between panic disorder and trauma-related conditioned fear, and update guidelines to reflect emerging evidence about peptide and endocannabinoid mechanisms. Research funding agencies could support small, well-designed clinical trials of peptide-pathway modulators in panic disorder and translational studies that measure biomarkers of peptide activity in humans. Public-health messaging should discourage self-medication with cannabis for PTSD until robust human data clarify benefits and risks, and instead promote evidence-based psychosocial supports available through community health centres. Finally, integrating culturally congruent interventions such as mindfulness-based programmes — which may engage endogenous peptide and neuromodulatory systems beneficially while resonating with Buddhist practices — could improve uptake and outcomes in Thai communities. ( Chemistry World feature: The chemistry of fear ) ( WHO country profile — Thailand )
The path from mouse circuits to Thai clinics is neither short nor certain, but the new peptide-focused map of fear narrows uncertainty and supplies testable targets. Policymakers and clinicians in Thailand can use these insights to prioritise research partnerships, refine clinical guidance, and scale culturally adapted psychosocial care while awaiting human trial data. For families and communities coping with trauma, the research offers hope: a clearer biochemical picture of fear opens the door to interventions that reduce panic, increase memory specificity, and restore safe daily life. ( Presynaptic sensor and silencer of peptidergic transmission, Cell 2024 ) ( A pontomesencephalic PACAPergic pathway underlying panic-like behaviour, PubMed/PMC ) ( Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice, Cell/Jan 2025 )
For Thai readers seeking practical steps now: if you or a family member experience recurrent panic or trauma-linked anxiety, seek care from a primary-care clinic or mental-health provider for assessment and evidence-based therapy. Ask clinicians about trauma-focused psychological treatments and caution around cannabis for PTSD. Community leaders and hospital administrators should lobby for training in trauma-informed care and for participation in translational research networks that can bring peptide-targeting trials to Thailand. These are realistic, culturally aligned actions that can accelerate the translation of exciting laboratory chemistry into better mental-health outcomes across Thai communities. ( WHO country profile — Thailand ) ( UNICEF Thailand mental-health country report )